Volume 11, Issue 5, January 29, 2019


CDC Science Clips: Volume 11, Issue 5, January 29, 2019

Science Clips is produced weekly to enhance awareness of emerging scientific knowledge for the public health community. Each article features an Altmetric Attention scoreExternal to track social and mainstream media mentions!

  1. Top Articles of the Week

    Selected weekly by a senior CDC scientist from the standard sections listed below.

    The names of CDC authors are indicated in bold text.
    • Chronic Diseases and Conditions
      • [No abstract]

      • Expansion of telestroke services improves quality of care provided in super rural areasExternal
        Zhang D, Wang G, Zhu W, Thapa JR, Switzer JA, Hess DC, Smith ML, Ritchey MD.
        Health Aff (Millwood). 2018 Dec;37(12):2005-2013.

        Telestroke is a telemedicine intervention that facilitates communication between stroke centers and lower-resourced facilities to optimize acute stroke management. Using administrative claims data, we assessed trends in telestroke use among fee-for-service Medicare beneficiaries with acute ischemic stroke and the association between providing telestroke services and intravenous tissue plasminogen activator (IV tPA) and mechanical thrombectomy use, mortality, and medical expenditures, by urban versus rural county of residence in the period 2008-15. The proportion of ischemic stroke cases receiving telestroke increased from 0.4 to 3.8 per 1,000 cases, with usage highest among younger, male, non-Hispanic white, and patients in rural or super rural areas (super rural is the bottom quartile of rural areas. Compared with patients receiving usual care, those receiving telestroke had greater IV tPA and mechanical thrombectomy use regardless of county type, while those in super rural counties had lower thirty-day all-cause mortality. Despite increased telestroke use, rural patients remained less likely than urban patients to receive IV tPA. The findings suggest that telestroke service expansion efforts have increased, especially in rural and super rural counties, and have improved outcomes.

    • Genetics and Genomics
      • Genome-wide association analyses of invasive pneumococcal isolates identify a missense bacterial mutation associated with meningitisExternal
        Li Y, Metcalf BJ, Chochua S, Li Z, Walker H, Tran T, Hawkins PA, Gierke R, Pilishvili T, McGee L, Beall BW.
        Nat Commun. 2019 Jan 14;10(1):178.

        Bacterial mutations predisposing pneumococcus to causing meningitis, a more severe form of invasive pneumococcal disease (IPD), are largely unknown. Knowledge of such mutations may improve our understanding of pathogenesis and inform preventive strategies. Here we report a pneumococcal pbp1b gene mutation (pbp1bA641C causing N214T change in PBP1b transglycosylase domain) that is associated with meningitis in an exploratory cohort of IPD patients (n = 2054, p = 6.8 x 10(-6)), in an independent confirmatory cohort (n = 2518, p = 2.3 x 10(-6)), and in a combined analysis (n = 4572, p = 3.0 x 10(-10)). Patients infected by the pbp1b641C genotype pneumococci show 2.8-fold odds (95% CI 1.7 to 4.8) of meningitis compared to those infected by non-pbp1b641C pneumococci, after controlling for pneumococcal serotype, antibiotic resistance, and patient age. The pbp1bA641C change results in longer time needed for bacterial killing by antibiotic treatment and shows evidence of being under positive selection. Thus, a pneumococcal mutation conferring increased antibiotic tolerance is associated with meningitis among IPD patients.

    • Immunity and Immunization
      • Provider time and costs to vaccinate adult patients: Impact of time counseling without vaccinationExternal
        Shen A, Khavjou O, King G, Bates L, Zhou F, Leidner AJ, Yarnoff B.
        Vaccine. 2019 Jan 10.

        Amid provider reports of financial barriers as an impediment to adult immunization, this study explores the time and costs of vaccination in adult provider practices. Both a Vaccination Time-Motion Study and Vaccine Practice Management Survey were conducted (March – October 2017) in a convenience sample of 19 family medicine (FM), internal medicine (IM), and obstetrician-gynecology (OBGYN) practices, in nine states. Practices were directly observed during a one week period; estimates were collected of time spent on activities that could not be directly observed. Cost estimates were calculated by converting staff time for performed activities. In the time-motion study, FM and IM practices spent similar time conducting vaccination activities (median=5min per vaccination), while OBGYN practices spent more time (median=29min per vaccination). Combining results from the time-motion study and the practice management survey, the median costs of vaccination remained similar for FM practices and IM practices at $7 and $8 per vaccination, respectively, but was substantially higher for OBGYN practices at $43 per vaccination. Factors that contributed to higher costs among OBGYN practices were the increased time to counsel patients, administer vaccines, and to plan and manage vaccine supplies. In addition, 68% of OBGYN patients who were offered and counseled to receive vaccines declined to receive them. Counseling patients who ultimately do not go on to receive a vaccine may be an important cost factor. Lower costs of vaccination services may be achieved by increasing efficiencies in workflow or the volume of vaccinations.

    • Laboratory Sciences
      • A real-time multiplex PCR assay for detection of Elizabethkingia species, and differentiating between E. anophelis and E. meningosepticaExternal
        Kelly AJ, Karpathy SE, Gulvik CA, Ivey ML, Whitney AM, Bell ME, Nicholson AC, Humrighouse BH, McQuiston JR.
        J Clin Microbiol. 2019 Jan 16.

        Nosocomial infections of Elizabethkingia species can have fatal outcomes if not identified and treated properly. The current diagnostic tools available require culture and isolation, which can extend the reporting time and delay treatment. Using comparative genomics, we developed an efficient multiplex real-time PCR for the simultaneous detection of all known species of Elizabethkingia, as well as differentiating the two most commonly reported species Elizabethkingia anophelis and Elizabethkingia meningoseptica.

      • An estimated 41,200 people were newly infected with hepatitis C virus (HCV) in 2016 in the United States. Screening tests for antibodies to HCV may generate up to 32% false positivity in low-risk populations. Current Centers for Disease Control and Prevention (CDC) screening recommendations do not require confirmatory testing of a screening anti-HCV positive test, however confirmation is valuable for surveillance in the absence of HCV RNA testing. Recombinant Immunoblot Assay (RIBA) was used as a confirmatory assay for anti-HCV reactive samples but was discontinued in 2013. Another anti-HCV confirmatory assay, INNO-LIA, is commercially available in Europe but not approved by the Food and Drug Administration (FDA) in the United States. We report the development of an anti-HCV assay performed on an automated immunoblot platform using a fourth generation HCV recombinant fusion protein. Based on testing of 70 well characterized samples of which 40 were HCV RNA and anti-HCV positive, 15 HCV RNA positive/anti-HCV negative and 15 HCV RNA and anti-HCV negative, the specificity and sensitivity of the HCV-WES assay was 100% and 95%, respectively. Concordance between INNO-LIA and HCV WES, was determined by testing 205 HCV RNA negative/anti-HCV positive samples, of which 149 (72.7%) were positive by HCV-WES, while 146 (71.2%) were positive by INNO-LIA. We have shown proof of concept for the use of this test for confirmation of screening anti-HCV results. The HCV-WES assay is advantageous over manual western blot assays and INNO-LIA including ease of use, low cost and reduced hands-on time.

    • Parasitic Diseases
      • The safety of atovaquone-proguanil for the prevention and treatment of malaria in pregnancy: A systematic reviewExternal
        Andrejko KL, Mayer RC, Kovacs S, Slutsker E, Bartlett E, Tan KR, Gutman JR.
        Travel Med Infect Dis. 2019 Jan 14.

        BACKGROUND: Malaria infection poses a significant risk in pregnancy, yet chemoprophylaxis for pregnant women is limited. A systematic review was conducted to evaluate the incidence of adverse outcomes after atovaquone-proguanil (AP) exposure during pregnancy. METHODS: Following PRISMA guidelines, the authors searched PubMed, MEDLINE, and the Malaria in Pregnancy Consortium Library to identify relevant literature including infant outcomes after exposure to atovaquone, proguanil, or AP in pregnancy. Two authors independently screened the titles, abstracts, and full texts, and extracted data into an EpiInfo database. Overall proportions and 95% confidence intervals of adverse outcomes were determined by pooling data across studies. RESULTS: Of 455 records identified, 16 studies were included: ten AP studies and six proguanil studies. The overall proportions and 95% confidence intervals (CI) of adverse outcomes reported for the 446 women exposed to AP include miscarriage (8.08% CI: 5.07, 12.08%), stillbirth (1.05% CI: 0.03, 5.73%), early neonatal death (0% CI: 0, 7.4%), and congenital anomalies (2.56% CI: 1.28, 4.53%). CONCLUSIONS: The limited available data suggest that outcomes following AP exposure during pregnancy are similar to expected rates in similar populations. AP may be a promising option for pregnant women, but further data are needed on its safety in pregnancy.

    • Substance Use and Abuse
      • Comparison of nicotine and toxicant exposure in users of electronic cigarettes and combustible cigarettesExternal
        Goniewicz ML, Smith DM, Edwards KC, Blount BC, Caldwell KL, Feng J, Wang L, Christensen C, Ambrose B, Borek N, van Bemmel D, Konkel K, Erives G, Stanton CA, Lambert E, Kimmel HL, Hatsukami D, Hecht SS, Niaura RS, Travers M, Lawrence C, Hyland AJ.
        JAMA Netw Open. 2018 Dec 7;1(8):e185937.

        Importance: Use of electronic cigarettes (e-cigarettes) is increasing. Measures of exposure to known tobacco-related toxicants among e-cigarette users will inform potential health risks to individual product users. Objectives: To estimate concentrations of tobacco-related toxicants among e-cigarette users and compare these biomarker concentrations with those observed in combustible cigarette users, dual users, and never tobacco users. Design, Setting, and Participants: A population-based, longitudinal cohort study was conducted in the United States in 2013-2014. Cross-sectional analysis was performed between November 4, 2016, and October 5, 2017, of biomarkers of exposure to tobacco-related toxicants collected by the Population Assessment of Tobacco and Health Study. Participants included adults who provided a urine sample and data on tobacco use (N = 5105). Exposures: The primary exposure was tobacco use, including current exclusive e-cigarette users (n = 247), current exclusive cigarette smokers (n = 2411), and users of both products (dual users) (n = 792) compared with never tobacco users (n = 1655). Main Outcomes and Measures: Geometric mean concentrations of 50 individual biomarkers from 5 major classes of tobacco product constituents were measured: nicotine, tobacco-specific nitrosamines (TSNAs), metals, polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs). Results: Of the 5105 participants, most were aged 35 to 54 years (weighted percentage, 38%; 95% CI, 35%-40%), women (60%; 95% CI, 59%-62%), and non-Hispanic white (61%; 95% CI, 58%-64%). Compared with exclusive e-cigarette users, never users had 19% to 81% significantly lower concentrations of biomarkers of exposure to nicotine, TSNAs, some metals (eg, cadmium and lead), and some VOCs (including acrylonitrile). Exclusive e-cigarette users showed 10% to 98% significantly lower concentrations of biomarkers of exposure, including TSNAs, PAHs, most VOCs, and nicotine, compared with exclusive cigarette smokers; concentrations were comparable for metals and 3 VOCs. Exclusive cigarette users showed 10% to 36% lower concentrations of several biomarkers than dual users. Frequency of cigarette use among dual users was positively correlated with nicotine and toxicant exposure. Conclusions and Relevance: Exclusive use of e-cigarettes appears to result in measurable exposure to known tobacco-related toxicants, generally at lower levels than cigarette smoking. Toxicant exposure is greatest among dual users, and frequency of combustible cigarette use is positively correlated with tobacco toxicant concentration. These findings provide evidence that using combusted tobacco cigarettes alone or in combination with e-cigarettes is associated with higher concentrations of potentially harmful tobacco constituents in comparison with using e-cigarettes alone.

    • Zoonotic and Vectorborne Diseases
      • Higher C6 enzyme immunoassay index values correlate with a diagnosis of noncutaneous Lyme diseaseExternal
        Nigrovic LE, Lipsett SC, Molins CR, Wormser GP, Bennett JE, Garro AC, Levas MN, Balamuth F, Neville D, Lingampalli N, Robinson WH, Branda JA.
        Diagn Microbiol Infect Dis. 2018 Dec 8.

        The correlation between the Food and Drug Administration-cleared C6 enzyme immunoassay (EIA) C6 index values and a diagnosis of Lyme disease has not been examined. We used pooled patient-level data from 5 studies of adults and children with Lyme disease and control subjects who were tested with the C6 EIA. We constructed a receiver operating characteristic curve using regression clustered by study and measured the area under the curve (AUC) to examine the accuracy of the C6 index values in differentiating between patients with noncutaneous Lyme disease and control subjects. In the 4821 included patients, the C6 index value had excellent ability to distinguish between patients with noncutaneous Lyme disease and control subjects [AUC 0.99; 95% confidence interval (CI) 0.99-1.00]. An index value cut point of >/=3.0 had a sensitivity of 90.9% (95% CI, 87.8-93.3) and specificity of 99.0% (95% CI, 98.6-99.2%) for Lyme disease.

  2. CDC Authored Publications
    The names of CDC authors are indicated in bold text.
    Articles published in the past 6-8 weeks authored by CDC or ATSDR staff.
    • Chronic Diseases and Conditions
      1. Racial disparities in the incidence of primary chronic cutaneous lupus erythematosus in the southeastern US: The Georgia Lupus RegistryExternal
        Drenkard C, Parker S, Aspey LD, Gordon C, Helmick CG, Bao G, Lim SS.
        Arthritis Care Res (Hoboken). 2019 Jan;71(1):95-103.

        OBJECTIVE: Relative to studies of systemic lupus erythematosus (SLE), epidemiologic studies of chronic cutaneous lupus erythematosus (CCLE) are rare and are limited to populations with no racial diversity. We sought to provide minimum estimates of the incidence of primary CCLE (CCLE in the absence of SLE) in a population comprised predominantly of white individuals and black individuals in the southeastern region of the US. METHODS: The Georgia Lupus Registry allowed for the use of multiple sources for case-finding, including dermatology and rheumatology practices, multispecialty health care facilities, and dermatopathology reports. Cases with a clinical or clinical/histologic diagnosis of CCLE were classified as definite. Cases ascertained exclusively from dermatopathology reports were categorized as probable. Age-standardized incidence rates stratified by sex and race were calculated for discoid lupus erythematosus (DLE) in particular and for CCLE in general. RESULTS: The overall age-adjusted estimates for combined (definite and probable) CCLE were 3.9 per 100,000 person-years (95% confidence interval [95% CI] 3.4-4.5). The overall age-adjusted incidences of definite and combined DLE were 2.9 (95% CI 2.4-3.4) and 3.7 (95% CI 3.2-4.3) per 100,000 person-years, respectively. When capture-recapture methods were used, the age-adjusted incidence of definite DLE increased to 4.0 (95% CI 3.2-4.3). The black:white and female:male incidence ratios for definite DLE were 5.4 and 3.1, respectively. CONCLUSION: Our findings underscore the striking racial disparities in susceptibility to primary CCLE, with black individuals having a 3-fold to 5-fold increased incidence of CCLE in general, and DLE in particular, compared with white individuals. The observed sex differences were consistent with those reported previously, with a 3 times higher risk of DLE in women compared with men.

      2. Cardiovascular risk factors associated with venous thromboembolismExternal
        Gregson J, Kaptoge S, Bolton T, Pennells L, Willeit P, Burgess S, Bell S, Sweeting M, Rimm EB, Kabrhel C, Zoller B, Assmann G, Gudnason V, Folsom AR, Arndt V, Fletcher A, Norman PE, Nordestgaard BG, Kitamura A, Mahmoodi BK, Whincup PH, Knuiman M, Salomaa V, Meisinger C, Koenig W, Kavousi M, Volzke H, Cooper JA, Ninomiya T, Casiglia E, Rodriguez B, Ben-Shlomo Y, Despres JP, Simons L, Barrett-Connor E, Bjorkelund C, Notdurfter M, Kromhout D, Price J, Sutherland SE, Sundstrom J, Kauhanen J, Gallacher J, Beulens JW, Dankner R, Cooper C, Giampaoli S, Deen JF, Gomez de la Camara A, Kuller LH, Rosengren A, Svensson PJ, Nagel D, Crespo CJ, Brenner H, Albertorio-Diaz JR, Atkins R, Brunner EJ, Shipley M, Njolstad I, Lawlor DA, van der Schouw YT, Selmer RM, Trevisan M, Verschuren WM, Greenland P, Wassertheil-Smoller S, Lowe GD, Wood AM, Butterworth AS, Thompson SG, Danesh J, Di Angelantonio E, Meade T.
        JAMA Cardiol. 2019 Jan 16.

        Importance: It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). Objective: To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. Design, Setting, and Participants: This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. Exposures: A panel of several established cardiovascular risk factors. Main Outcomes and Measures: Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). Results: Of the 731728 participants from the ERFC, 403396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421537 participants from the UK Biobank, 233699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. Conclusions and Relevance: Older age, smoking, and adiposity were consistently associated with higher VTE risk.

    • Communicable Diseases
      1. Notes from the Field: Tuberculosis control in the Aftermath of Hurricane Maria – Puerto Rico, 2017External
        Aboukheir MK, Alvarado-Ramy F, Fernandez Vazquez M, Joglar O.
        MMWR Morb Mortal Wkly Rep. 2019 Jan 18;68(2):46-47.

        [No abstract]

      2. Retention in HIV care among participants in the Patient-Centered HIV Care Model: A collaboration between community-based pharmacists and primary medical providersExternal
        Byrd KK, Hardnett F, Clay PG, Delpino A, Hazen R, Shankle MD, Camp NM, Suzuki S, Weidle PJ.
        AIDS Patient Care STDS. 2019 Jan 16.

        Poor retention in HIV care is associated with higher morbidity and mortality and greater risk of HIV transmission. The Patient-Centered HIV Care Model (PCHCM) integrated community-based pharmacists with medical providers. The model required sharing of patient clinical information and collaborative therapy-related action planning. The proportion of persons retained in care (>/=1 medical visit in each 6-month period of a 12-month measurement period with >/=60 days between visits), pre- and post-PCHCM implementation, was modeled using log binomial regression. Factors associated with post-implementation retention were determined using multi-variable regression. Of 765 enrolled persons, the plurality were male (n = 555) and non-Hispanic black (n = 331), with a median age of 48 years (interquartile range = 38-55); 680 and 625 persons were included in the pre- and post-implementation analyses, respectively. Overall, retention improved 12.9% (60.7-68.5%, p = 0.002). The largest improvement was seen among non-Hispanic black persons, 22.6% increase (59.7-73.2%, p < 0.001). Persons who were non-Hispanic black [adjusted risk ratio (ARR) 1.27, 95% confidence interval (CI) 1.08-1.48] received one or more pharmacist-clinic developed action plan (ARR 1.51, 95% CI 1.18-1.93), had three or more pharmacist encounters (ARR 1.17, 95% CI 1.05-1.30), were more likely to be retained post-implementation. In the final multi-variable models, only race/ethnicity [non-Hispanic black (ARR 1.27, 95% CI 1.09-1.48) and “other or unknown” race/ethnicity (ARR 1.36, 95% CI 1.14-1.63)] showed an association with post-implementation retention. PCHCM demonstrated how collaborations between community-based pharmacists and primary medical providers can improve retention in HIV care. This care model may be particularly useful for non-Hispanic black persons who often are less likely to be retained in care.

      3. Accelerating the elimination of viral hepatitis: a Lancet Gastroenterology & Hepatology CommissionExternal
        Cooke GS, Andrieux-Meyer I, Applegate TL, Atun R, Burry JR, Cheinquer H, Dusheiko G, Feld JJ, Gore C, Griswold MG, Hamid S, Hellard ME, Hou J, Howell J, Jia J, Kravchenko N, Lazarus JV, Lemoine M, Lesi OA, Maistat L, McMahon BJ, Razavi H, Roberts TR, Simmons B, Sonderup MW, Spearman CW, Taylor BE, Thomas DL, Waked I, Ward JW, Wiktor SZ.
        Lancet Gastroenterol Hepatol. 2019 Feb;4(2):135-184.

        Viral hepatitis is a major public health threat and a leading cause of death worldwide. Annual mortality from viral hepatitis is similar to that of other major infectious diseases such as HIV and tuberculosis. Highly effective prevention measures and treatments have made the global elimination of viral hepatitis a realistic goal, endorsed by all WHO member states. Ambitious targets call for a global reduction in hepatitis-related mortality of 65% and a 90% reduction in new infections by 2030. This Commission draws together a wide range of expertise to appraise the current global situation and to identify priorities globally, regionally, and nationally needed to accelerate progress. We identify 20 heavily burdened countries that account for over 75% of the global burden of viral hepatitis. Key recommendations include a greater focus on national progress towards elimination with support given, if necessary, through innovative financing measures to ensure elimination programmes are fully funded by 2020. In addition to further measures to improve access to vaccination and treatment, greater attention needs to be paid to access to affordable, high-quality diagnostics if testing is to reach the levels needed to achieve elimination goals. Simplified, decentralised models of care removing requirements for specialised prescribing will be required to reach those in need, together with sustained efforts to tackle stigma and discrimination. We identify key examples of the progress that has already been made in many countries throughout the world, demonstrating that sustained and coordinated efforts can be successful in achieving the WHO elimination goals.

      4. The HCV care continuum: linkage to HCV care and treatment among patients at an urban health network, Philadelphia, PAExternal
        Coyle C, Moorman AC, Bartholomew T, Klein G, Kwakwa H, Mehta SH, Holtzman D.
        Hepatology. 2019 Jan 11.

        BACKGROUND/AIMS: Improving care and treatment for persons infected with hepatitis C virus (HCV) can reduce HCV-related morbidity and mortality. Our primary objective was to examine the HCV care continuum among patients receiving care at five Federally Qualified Health Centers (FQHCs) in Philadelphia, PA where a testing and linkage to care program had been established. METHODS: Among the five FQHCs, one served a homeless population, two served public housing residents, one served a majority Hispanic population, and the last, a “test and treat” site, also provided HCV treatment to patients. We analyzed data from electronic health records of patients tested for HCV antibody from 2012-2016 and calculated the percentage of patients across nine steps of the HCV care continuum ranging from diagnosis to cure. We further explored factors associated with successful patient navigation through two steps of the continuum using multivariable logistic regression. RESULTS: Of 885 chronically infected patients, 92.2% received their RNA positive result, 82.7% were referred to an HCV provider, 69.4% were medically evaluated by the provider, 55.3% underwent liver disease staging, 15.0% initiated treatment, 12.0% completed treatment, 8.7% were assessed for sustained virologic response (SVR), and 8.0% achieved SVR. Regression results revealed that test and treat site patients were significantly more likely to be medically evaluated (aOR=2.76; 95% CI=1.82, 4.17) and undergo liver disease staging (aOR=1.92, 95% CI=1.02, 2.86) than patients at the other FQHCs combined. CONCLUSIONS: In this U.S. urban setting, over two-thirds of HCV-infected patients were linked to care. Although treatment uptake was low overall, it was highest at the test and treat site. Scaling up treatment services in HCV testing settings will be vital to improve the HCV care continuum. This article is protected by copyright. All rights reserved.

      5. Outpatient antibiotic prescribing for acute respiratory infections during influenza seasonsExternal
        Havers FP, Hicks LA, Chung JR, Gaglani M, Murthy K, Zimmerman RK, Jackson LA, Petrie JG, McLean HQ, Nowalk MP, Jackson ML, Monto AS, Belongia EA, Flannery B, Fry AM.
        JAMA Netw Open. 2018 Jun 1;1(2):e180243.

        Importance: Acute respiratory infections (ARIs) are the syndrome for which antibiotics are most commonly prescribed; viruses for which antibiotics are ineffective cause most ARIs. Objectives: To characterize antibiotic prescribing among outpatients with ARI during influenza season and to identify targets for reducing inappropriate antibiotic prescribing for common ARI diagnoses, including among outpatients with laboratory-confirmed influenza. Design, Setting, and Participants: Cohort study enrolling outpatients aged 6 months or older with ARI evaluated at outpatient clinics associated with 5 US Influenza Vaccine Effectiveness Network sites during the 2013-2014 and 2014-2015 influenza seasons. All patients received influenza testing by real-time reverse transcriptase-polymerase chain reaction for research purposes only. Antibiotic prescriptions, medical history, and International Classification of Diseases, Ninth Revision diagnosis codes were collected from medical and pharmacy records, as were group A streptococcal (GAS) testing results in a patient subset. Exposure: Visit for ARI, defined by a new cough of 7 days’ duration or less. Main Outcomes and Measures: Antibiotic prescription within 7 days of enrollment. Appropriateness of antibiotic prescribing was based on diagnosis codes, clinical information, and influenza and GAS testing results. Results: Of 14987 patients with ARI (mean [SD] age, 32 [24] years; 8638 [58%] women; 11892 [80%] white), 6136 (41%) were prescribed an antibiotic. Among these 6136 patients, 2522 (41%) had diagnoses for which antibiotics are not indicated; 2106 (84%) of these patients were diagnosed as having a viral upper respiratory tract infection or bronchitis (acute or not otherwise specified). Among the 3306 patients (22%) not diagnosed as having pneumonia and who had laboratory-confirmed influenza, 945 (29%) were prescribed an antibiotic, accounting for 17% of all antibiotic prescriptions among patients with nonpneumonia ARI. Among 1248 patients with pharyngitis, 1137 (91%) had GAS testing; 440 of the 1248 patients (35%) were prescribed antibiotics, among whom 168 (38%) had negative results on GAS testing. Of 1200 patients with sinusitis and no other indication for antibiotic treatment who received an antibiotic, 454 (38%) had symptoms for 3 days or less prior to the outpatient visit, suggesting acute viral sinusitis not requiring antibiotics. Conclusions and Relevance: Antibiotic overuse remains widespread in the treatment of outpatient ARIs, including among patients with laboratory-confirmed influenza, although study sites may not be representative of other outpatient settings. Identified targets for improved outpatient antibiotic stewardship include eliminating antibiotic treatment of viral upper respiratory tract infections and bronchitis and improving adherence to prescribing guidelines for pharyngitis and sinusitis. Increased access to sensitive and timely virus diagnostic tests, particularly for influenza, may reduce unnecessary antibiotic use for these syndromes.

      6. Undisclosed HIV infection among men who have sex with men in National HIV Behavioral Surveillance, 2014External
        Hoots BE, Wejnert C, Martin A, Haaland R, Masciotra S, Sionean C, Smith A, Switzer WM, Paz-Bailey G.
        Aids. 2019 Jan 14.

        OBJECTIVE: As a proxy for undiagnosed HIV, CDC’s National HIV Behavioral Surveillance (NHBS) monitors participants who report being unaware of their infection, defined as self-reporting an HIV-negative or unknown status during the interview but testing positive for HIV infection. We validated the NHBS measure of awareness among men who have sex with men (MSM) in 2014. DESIGN: We tested dried blood spots (DBS) from MSM who reported being unaware of their infection for seven antiretrovirals (ARVs). MSM unaware with >/=1 ARV detected were defined as misreporters. METHODS: Weighted percentages and 95% confidence intervals were calculated to compare characteristics among misreporters, non-misreporters, and those who self-reported as HIV-positive. Viral load (VL) was quantified with a validated assay using DBS. RESULTS: Of 1,818 HIV-positive MSM, 299 (16%) self-reported as HIV-negative or unknown infection status. Of these 299, 145 (49%) were considered misreporters based on ARV detection. Among the unaware, misreporters were more likely than non-misreporters to be older and have health insurance. Compared to self-reported HIV-positive MSM, misreporters were more likely to be black, be bisexual, and have perceived discrimination. Of 138 misreporters with VL data, 116 (84%) had an undetectable VL. CONCLUSIONS: ARV testing revealed that half of MSM classified as unaware of their infection misreported their status. While off-label PrEP use might explain the presence of ARVs, it is unlikely since many misreporters were virally suppressed, suggesting they were on HIV therapy. Biomarker validation of behavioral data can improve data quality and usefulness in NHBS and other studies.

      7. Estimating prevalent diagnoses and rates of new diagnoses of HIV at the state level by age group among men who have sex with men in the United StatesExternal
        Jones J, Grey JA, Purcell DW, Bernstein KT, Sullivan PS, Rosenberg ES.
        Open Forum Infect Dis. 2018 Jun;5(6):ofy124.

        Background: Men who have sex with men (MSM) in the United States experience a disproportionate rate of diagnosis of HIV. Surveillance data demonstrate age-based disparities among MSM, with higher rates of diagnosis among MSM age </=34 years nationally. Population size estimates within age group at the state level have not been available to determine rates for each state. We estimated the size of the MSM population in 5 age groups in each state and estimated the rate of prevalent HIV diagnoses in 2013 and new HIV diagnoses in 2014. Methods: We used data from the General Social Survey, American Community Survey, and previously published estimates from the National Health and Nutrition Examination Survey to estimate the population of MSM in 5 age groups at the state level. We combined these estimates with surveillance data to estimate age-stratified rates of prevalent diagnoses in 2013 and new diagnoses in 2014 in each state. We estimated standardized prevalence and diagnosis ratios comparing the Northeast, South, and West regions with the Midwest. Results: Rates of prevalent diagnoses increased with increasing age, and rates of new diagnoses were highest among younger age groups. In the United States, the new diagnosis rate among those age 18-24 years in 2014 was 1.4 per 100 MSM without a diagnosis. The highest diagnosis rates were observed among men age </=34 years in the South. Conclusions: Age-stratified estimates of HIV prevalence and new diagnosis rates at the state level can inform public health prevention strategies and resource allocation.

      8. BACKGROUND: Neonatal herpes (nHSV) is a potentially fatal disease caused by herpes simplex virus (HSV) infection during the neonatal period. Neonatal herpes simplex virus infections are not nationally notifiable, and varying incidence rates have been reported. Beginning in 2006, New York City (NYC) required reporting of nHSV infections and conducted case investigations. We compared the use of administrative hospital data with active surveillance to monitor trends in nHSV infection. METHODS: We compared the incidence and characteristics of nHSV cases as measured using population-based surveillance and administrative hospital discharge data collected between 2006 and 2015. Surveillance cases were defined as laboratory-confirmed HSV infections in NYC-resident infants aged 60 days or younger at diagnosis. Administrative cases were defined as NYC-resident infants aged 60 days or younger at hospital admission whose records included an HSV diagnosis. Neonatal herpes cases after ritual Jewish circumcision with direct orogenital suction were excluded. RESULTS: There were 107 surveillance cases (9.9 per 100,000 live births) and 131 administrative cases (12.1 per 100,000 live births). Incidence was highest in infants born to non-Hispanic black mothers aged 20 years or younger (surveillance, 57.2 per 100,000 live births; administrative data, 31.2 per 100,000 live births). The distribution of cases by year did not significantly differ across data sources. Surveillance cases had a higher case-fatality rate (18.7%) compared with administrative cases (8.4%; P = 0.019). CONCLUSIONS: Administrative hospital data can be used to measure the incidence of nHSV infection and describe disease burden across population subgroups in jurisdictions where nHSV reporting is not required. However, administrative data may underascertain nHSV case fatality.

      9. Sustained virological response to hepatitis C treatment decreases the incidence of complications associated with type 2 diabetesExternal
        Li J, Gordon SC, Rupp LB, Zhang T, Trudeau S, Holmberg SD, Moorman AC, Spradling PR, Teshale EH, Boscarino JA, Schmidt MA, Daida YG, Lu M.
        Aliment Pharmacol Ther. 2019 Jan 16.

        BACKGROUND: The role of hepatitis C (HCV) eradication on the long-term complications of type 2 diabetes mellitus remains incompletely studied. AIM: We investigated whether antiviral treatment impacted risk of acute coronary syndrome, end-stage renal disease, ischaemic stroke, and retinopathy among diabetic patients from the four US health systems comprising the Chronic Hepatitis Cohort Study (CHeCS). METHODS: We included CHeCS HCV patients with diagnosis codes for type 2 diabetes who were on antidiabetic medications. Patients were followed until an outcome of interest, death, or last health system encounter. The effect of treatment on outcomes was estimated using the competing risk analysis (Fine-Gray subdistribution hazard ratio [sHR]), with death as a competing event. RESULTS: Among 1395 HCV-infected patients with type 2 diabetes, 723 (52%) were treated with either interferon-based or direct-acting antivirals (DAAs); 539 (75% of treated) achieved sustained virological response (SVR). After propensity score adjustment to address treatment selection bias, patients with SVR demonstrated significantly decreased risk of acute coronary syndrome (sHR = 0.36; P < 0.001), end-stage renal disease (sHR = 0.46; P < 0.001), stroke (sHR = 0.34; P < 0.001), and retinopathy (sHR = 0.24; P < 0.001) compared to untreated patients. Results were consistent in subgroup analyses of DAA-treated patients and interferon-treated patients, an analysis of cirrhotic patients, as well as in sensitivity analyses considering cause-specific hazards, exclusion of patients with on-treatment retinopathy, and treatment status as a time-varying covariate. CONCLUSION: Successful HCV treatment among patients with type 2 diabetes significantly reduces incidence of acute coronary syndrome, end-stage renal disease, ischaemic stroke, and retinopathy, regardless of cirrhosis. Our findings support the importance of HCV antiviral therapy among patients with type 2 diabetes to reduce the risk of these extrahepatic outcomes.

      10. High levels of HIV-1 drug resistance in children who acquired HIV infection through mother to child transmission in the era of Option B+, Haiti, 2013-2014External
        Louis FJ, Segaren N, Desinor O, Beard RS, Jean-Louis R, Chang J, Boisson S, Hulland EN, Wagar N, DeVos J, Francois K, Buteau J, Boncy J, Marston BJ, Domercant JW, Yang C, Charles M.
        Pediatr Infect Dis J. 2018 Dec 27.

        BACKGROUND: The main objective of this study was to determine the frequency and patterns of HIVDR-associated mutations among children <18 months old born to HIV-1-positive mothers enrolled in the prevention of mother-to-child transmission (PMTCT) services in Haiti. METHODS: Between January 1, 2013 and December 31, 2014, HIV-positive remnant dried blood spots (DBS) collected from children under 18 months old for Early Infant Diagnosis (EID) at the National Public Health Laboratory were used for HIV-1 genotyping. HIVDR mutations were analyzed using the Stanford Drug Resistance HIVdb program. RESULTS: Of the 3,555 DBS collected for EID, 360 (10.1%) were HIV-positive and 355 were available for genotyping. Of these, 304 (85.6%) were successfully genotyped and 217 (71.4%) had >/= one DR mutation. Mutations conferring resistance to NRTIs and NNRTIs were present in 40.5% (123) and 69.1% (210), respectively. The most frequent mutations were K103N/S (48.0%), M184V (37.5%), and G190A/S (15.1%), and Y181C/G/V (14.1%). Predicted drug resistance analysis revealed that 68.8% of the children had high-level resistance to NNRTIs and 11.5% had intermediate to high-level resistance to abacavir. CONCLUSIONS: This study showed high rates of resistance to NRTIs and NNRTIs among newly HIV-diagnosed children in Haiti, suggesting that in the era of “option B+” (initiation of lifelong combination antiretroviral therapy to pregnant women with HIV), the majority of children who acquire HIV infection through MTCT have resistant HIV. These results have led the National HIV Program to revise the pediatric guidelines to include protease inhibitors in first-line regimens for all HIV-positive newborns.

      11. Association between severe drought and HIV prevention and care behaviors in Lesotho: A population-based survey 2016-2017External
        Low AJ, Frederix K, McCracken S, Manyau S, Gummerson E, Radin E, Davia S, Longwe H, Ahmed N, Parekh B, Findley S, Schwitters A.
        PLoS Med. 2019 Jan;16(1):e1002727.

        BACKGROUND: A previous analysis of the impact of drought in Africa on HIV demonstrated an 11% greater prevalence in HIV-endemic rural areas attributable to local rainfall shocks. The Lesotho Population-Based HIV Impact Assessment (LePHIA) was conducted after the severe drought of 2014-2016, allowing for reevaluation of this relationship in a setting of expanded antiretroviral coverage. METHODS AND FINDINGS: LePHIA selected a nationally representative sample between November 2016 and May 2017. All adults aged 15-59 years in randomly selected households were invited to complete an interview and HIV testing, with one woman per household eligible to answer questions on their experience of sexual violence. Deviations in rainfall for May 2014-June 2016 were estimated using precipitation data from Climate Hazards Group InfraRed Precipitation with Station Data (CHIRPS), with drought defined as <15% of the average rainfall from 1981 to 2016. The association between drought and risk behaviors as well as HIV-related outcomes was assessed using logistic regression, incorporating complex survey weights. Analyses were stratified by age, sex, and geography (urban versus rural). All of Lesotho suffered from reduced rainfall, with regions receiving 1%-36% of their historical rainfall. Of the 12,887 interviewed participants, 93.5% (12,052) lived in areas that experienced drought, with the majority in rural areas (7,281 versus 4,771 in urban areas). Of the 835 adults living in areas without drought, 520 were in rural areas and 315 in urban. Among females 15-19 years old, living in a rural drought area was associated with early sexual debut (odds ratio [OR] 3.11, 95% confidence interval [CI] 1.43-6.74, p = 0.004), and higher HIV prevalence (OR 2.77, 95% CI 1.19-6.47, p = 0.02). It was also associated with lower educational attainment in rural females ages 15-24 years (OR 0.44, 95% CI 0.25-0.78, p = 0.005). Multivariable analysis adjusting for household wealth and sexual behavior showed that experiencing drought increased the odds of HIV infection among females 15-24 years old (adjusted OR [aOR] 1.80, 95% CI 0.96-3.39, p = 0.07), although this was not statistically significant. Migration was associated with 2-fold higher odds of HIV infection in young people (aOR 2.06, 95% CI 1.25-3.40, p = 0.006). The study was limited by the extensiveness of the drought and the small number of participants in the comparison group. CONCLUSIONS: Drought in Lesotho was associated with higher HIV prevalence in girls 15-19 years old in rural areas and with lower educational attainment and riskier sexual behavior in rural females 15-24 years old. Policy-makers may consider adopting potential mechanisms to mitigate the impact of income shock from natural disasters on populations vulnerable to HIV transmission.

      12. Improved state-level influenza nowcasting in the United States leveraging Internet-based data and network approachesExternal
        Lu FS, Hattab MW, Clemente CL, Biggerstaff M, Santillana M.
        Nat Commun. 2019 Jan 11;10(1):147.

        In the presence of health threats, precision public health approaches aim to provide targeted, timely, and population-specific interventions. Accurate surveillance methodologies that can estimate infectious disease activity ahead of official healthcare-based reports, at relevant spatial resolutions, are important for achieving this goal. Here we introduce a methodological framework which dynamically combines two distinct influenza tracking techniques, using an ensemble machine learning approach, to achieve improved state-level influenza activity estimates in the United States. The two predictive techniques behind the ensemble utilize (1) a self-correcting statistical method combining influenza-related Google search frequencies, information from electronic health records, and historical flu trends within each state, and (2) a network-based approach leveraging spatio-temporal synchronicities observed in historical influenza activity across states. The ensemble considerably outperforms each component method in addition to previously proposed state-specific methods for influenza tracking, with higher correlations and lower prediction errors.

      13. Epidemiology of invasive early-onset and late-onset group B streptococcal disease in the United States, 2006 to 2015: Multistate laboratory and population-based surveillanceExternal
        Nanduri SA, Petit S, Smelser C, Apostol M, Alden NB, Harrison LH, Lynfield R, Vagnone PS, Burzlaff K, Spina NL, Dufort EM, Schaffner WS, Thomas AR, Farley MM, Jain JH, Pondo T, McGee L, Beall BW, Schrag SJ.
        JAMA Pediatr. 2019 Jan 14.

        Importance: Invasive disease owing to group B Streptococcus (GBS) remains an important cause of illness and death among infants younger than 90 days in the United States, despite declines in early-onset disease (EOD; with onset at 0-6 days of life) that are attributed to intrapartum antibiotic prophylaxis (IAP). Maternal vaccines to prevent infant GBS disease are currently under development. Objective: To describe incidence rates, case characteristics, antimicrobial resistance, and serotype distribution of EOD and late-onset disease (LOD; with onset at 7-89 days of life) in the United States from 2006 to 2015 to inform IAP guidelines and vaccine development. Design, Setting, and Participants: This study used active population-based and laboratory-based surveillance for invasive GBS disease conducted through Active Bacterial Core surveillance in selected counties of 10 states across the United States. Residents of Active Bacterial Core surveillance areas who were younger than 90 days and had invasive GBS disease in 2006 to 2015 were included. Data were analyzed from December 2017 to April 2018. Exposures: Group B Streptococcus isolated from a normally sterile site. Main Outcomes and Measures: Early-onset disease and LOD incidence rates and associated GBS serotypes and antimicrobial resistance. Results: The Active Bacterial Core surveillance program identified 1277 cases of EOD and 1387 cases of LOD. From 2006 to 2015, EOD incidence declined significantly from 0.37 to 0.23 per 1000 live births (P < .001), and LOD rates remained stable (mean, 0.31 per 1000 live births). Among the mothers of 1277 infants with EOD, 617 (48.3%) had no indications for IAP and did not receive it, and 278 (21.8%) failed to receive IAP despite having indications. Serotype data were available for 1743 of 1897 patients (91.3%) from 7 sites that collect GBS isolates. Among these isolates, serotypes Ia (242 [27.3%]) and III (242 [27.3%]) were most common. Among patients with LOD, serotype III was most common (481 [56.2%]), and this increased from 2006 to 2015 from 0.12 to 0.20 cases per 1000 live births (P < .001). Serotype IV caused 53 cases (6.2%) of EOD and LOD combined. The 6 most common serotypes (Ia, Ib, II, III, IV, and V) caused 881 EOD cases (99.3%) and 853 LOD cases (99.7%). No beta-lactam resistance was identified; 359 isolates (20.8%) tested showed constitutive clindamycin resistance. In 2015, an estimated 840 EOD cases and 1265 LOD cases occurred nationally. Conclusions and Relevance: The rates of LOD among US infants are now higher than EOD rates. Combined with addressing IAP implementation gaps, an effective vaccine covering the most common serotypes might further reduce EOD rates and help prevent LOD, for which there is no current public health intervention.

      14. Notes from the Field: Typhoid fever outbreak – Harare, Zimbabwe, October 2017-February 2018External
        N’Cho H S, Masunda KP, Mukeredzi I, Manangazira P, Govore E, Duri C, Aubert RD, Martin H, Gonese E, Vere M, Tippett Barr BA, Balachandra S, Strysko J, Davis WW, Appiah GD, Mintz E.
        MMWR Morb Mortal Wkly Rep. 2019 Jan 18;68(2):44-45.

        [No abstract]

      15. Determining the cause of death among children hospitalized with respiratory illness in Kenya: Protocol for Pediatric Respiratory Etiology Surveillance Study (PRESS)External
        Njuguna HN, Zaki SR, Roberts DJ, Fligner CL, Keating MK, Rogena E, Walong E, Gachii AK, Maleche-Obimbo E, Irimu G, Mathaiya J, Orata N, Lopokoiyit R, Maina J, Emukule GO, Onyango CO, Gikunju S, Owuor C, Kinuthia P, Bunei M, Fields B, Widdowson MA, Mott JA, Chaves SS.
        JMIR Res Protoc. 2019 Jan 10;8(1):e10854.

        BACKGROUND: In sub-Saharan Africa, where the burden of respiratory disease-related deaths is the highest, information on the cause of death remains inadequate because of poor access to health care and limited availability of diagnostic tools. Postmortem examination can aid in the ascertainment of causes of death. This manuscript describes the study protocol for the Pediatric Respiratory Etiology Surveillance Study (PRESS). OBJECTIVE: This study protocol aims to identify causes and etiologies associated with respiratory disease-related deaths among children (age 1-59 months) with respiratory illness admitted to the Kenyatta National Hospital (KNH), the largest public hospital in Kenya, through postmortem examination coupled with innovative approaches to laboratory investigation. METHODS: We prospectively followed children hospitalized with respiratory illness until the end of clinical care or death. In case of death, parents or guardians were offered grief counseling, and postmortem examination was offered. Lung tissue specimens were collected using minimally invasive tissue sampling and conventional autopsy where other tissues were collected. Tissues were tested using histopathology, immunohistochemistry, and multipathogen molecular-based assays to identify pathogens. For each case, clinical and laboratory data were reviewed by a team of pathologists, clinicians, laboratorians, and epidemiologists to assign a cause of and etiology associated with death. RESULTS: We have enrolled pediatric cases of respiratory illness hospitalized at the KNH at the time of this submission; of those, 14.8% (140/945) died while in the hospital. Both analysis and interpretation of laboratory results and writing up of findings are expected in 2019-2020. CONCLUSIONS: Postmortem studies can help identify major pathogens contributing to respiratory-associated deaths in children. This information is needed to develop evidence-based prevention and treatment policies that target important causes of pediatric respiratory mortality and assist with the prioritization of local resources. Furthermore, PRESS can provide insights into the interpretation of results using multipathogen testing platforms in resource-limited settings. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/10854.

      16. PrEP awareness in the context of HIV/AIDS conspiracy beliefs among black/African American and Hispanic/Latino MSM in three urban US citiesExternal
        Olansky E, Mansergh G, Pitts N, Mimiaga MJ, Denson DJ, Landers S, Holman J, Herbst JH.
        J Homosex. 2019 Jan 11:1-11.

        We examined HIV conspiracy beliefs and PrEP awareness in a convenience sample of minority MSM. Participants in three cities completed a behavioral self-assessment on sociodemographics, PrEP awareness, and HIV/AIDS conspiracy beliefs. HIV/AIDS conspiracy beliefs were more common among Black than Latino MSM (58% vs. 42%, p < .05), and among younger men than older men (age 18-29 (50%), 30-39 (22%), 40+ (28%); p < .05). PrEP awareness co-occurred with conspiracy belief less (37%) than with non-belief (63%, p < .05), persisting in multivariable regression (aOR = 0.52, 95% CI = 0.38-0.71). This relationship suggests that current HIV care and prevention messaging is either inaccessible or not credible to some minority subpopulations.

      17. Rates of hospitalization and death for all-cause and rotavirus acute gastroenteritis before rotavirus vaccine introduction in Kenya, 2010-2013External
        Omore R, Khagayi S, Ogwel B, Onkoba R, Ochieng JB, Juma J, Munga S, Tabu C, Kibet S, Nuorti JP, Odhiambo F, Mwenda JM, Breiman RF, Parashar UD, Tate JE.
        BMC Infect Dis. 2019 Jan 11;19(1):47.

        BACKGROUND: Rotavirus vaccine was introduced in Kenya immunization program in July 2014. Pre-vaccine disease burden estimates are important for assessing vaccine impact. METHODS: Children with acute gastroenteritis (AGE) (>/=3 loose stools and/or >/= 1 episode of unexplained vomiting followed by loose stool within a 24-h period), hospitalized in Siaya County Referral Hospital (SCRH) from January 2010 through December 2013 were enrolled. Stool specimens were tested for rotavirus (RV) using an enzyme immunoassay (EIA). Hospitalization rates were calculated using person-years of observation (PYO) from the Health Demographic Surveillance System (HDSS) as a denominator, while adjusting for healthcare utilization at household level and proportion of stool specimen collected from patients who met the case definition at the surveillance hospital. Mortality rates were calculated using PYO as the denominator and number of deaths estimated using total deaths in the HDSS, proportion of deaths attributed to diarrhoea by verbal autopsy (VA) and percent positive for rotavirus AGE (RVAGE) hospitalizations. RESULTS: Of 7760 all-cause hospitalizations among children < 5 years of age, 3793 (49%) were included in the analysis. Of these, 21% (805) had AGE; RV was detected in 143 (26%) of 541 stools tested. Among children < 5 years, the estimated hospitalization rates per 100,000 PYO for AGE and RVAGE were 2413 and 429, respectively. Mortality rate associated with AGE and RVAGE were 176 and 45 per 100,000 PYO, respectively. CONCLUSION: AGE and RVAGE caused substantial health care burden (hospitalizations and deaths) before rotavirus vaccine introduction in Kenya.

      18. Evaluation of an adapted project connect community based intervention among professionals serving young minority menExternal
        Perin J, Jennings JM, Arrington-Sanders R, Page KR, Loosier PS, Dittus PJ, Marcell AV.
        Sex Transm Dis. 2019 Jan 15.

        BACKGROUND: To address sexual and reproductive health (SRH) needs of young minority urban males, we developed and evaluated Project Connect Baltimore (Connect), which was adapted from a program with demonstrated effectiveness among young females. The objectives were to determine 1) the feasibility of Connect as adapted for young minority men, 2) whether the program increased SRH knowledge and resource sharing of youth-serving professionals (YSPs) working with young men, and 3) whether the program improved awareness and use of resources for young minority men in Baltimore City, an urban environment with high rates of STDs.MethodsConnect developed a clinic referral guide for male youth-friendly resources for SRH. YSPs working with partners and organizations serving young minority men were trained to use Connect materials and pre-, immediate-, and three-month post-training surveys were conducted to evaluate program effects. A before-after evaluation study was conducted among young men attending five urban Connect clinics where STD/HIV rates are high, recruiting young men in repeated cross-sectional surveys from April 2014 to September 2017. RESULTS: 235 YSPs were trained to use Connect materials, including a website, a paper-based pocket guide, and information regarding SRH for young men. These professionals demonstrated increased knowledge about SRH for young men at immediate post-test (60.6% to 86.7%, p<0.05), and reported more sharing of websites for SRH (23% to 62%, p<0.05) from pre- to three-month post-training. 169 young minority men were surveyed and reported increased awareness of Connect over three and a half years (4% to 11%, p=0.015), although few young men reported using the website to visit clinics. CONCLUSION: Project Connect Baltimore increased knowledge of SRH needs among youth-serving professionals and sharing of SRH resources by these professionals with young men. This program also demonstrated increases in awareness of SRH resources among young minority urban men.

      19. A collaborative multiyear, multimodel assessment of seasonal influenza forecasting in the United StatesExternal
        Reich NG, Brooks LC, Fox SJ, Kandula S, McGowan CJ, Moore E, Osthus D, Ray EL, Tushar A, Yamana TK, Biggerstaff M, Johansson MA, Rosenfeld R, Shaman J.
        Proc Natl Acad Sci U S A. 2019 Jan 15.

        Influenza infects an estimated 9-35 million individuals each year in the United States and is a contributing cause for between 12,000 and 56,000 deaths annually. Seasonal outbreaks of influenza are common in temperate regions of the world, with highest incidence typically occurring in colder and drier months of the year. Real-time forecasts of influenza transmission can inform public health response to outbreaks. We present the results of a multiinstitution collaborative effort to standardize the collection and evaluation of forecasting models for influenza in the United States for the 2010/2011 through 2016/2017 influenza seasons. For these seven seasons, we assembled weekly real-time forecasts of seven targets of public health interest from 22 different models. We compared forecast accuracy of each model relative to a historical baseline seasonal average. Across all regions of the United States, over half of the models showed consistently better performance than the historical baseline when forecasting incidence of influenza-like illness 1 wk, 2 wk, and 3 wk ahead of available data and when forecasting the timing and magnitude of the seasonal peak. In some regions, delays in data reporting were strongly and negatively associated with forecast accuracy. More timely reporting and an improved overall accessibility to novel and traditional data sources are needed to improve forecasting accuracy and its integration with real-time public health decision making.

      20. Prevalence of hepatitis C virus infection in US states and the District of Columbia, 2013 to 2016External
        Rosenberg ES, Rosenthal EM, Hall EW, Barker L, Hofmeister MG, Sullivan PS, Dietz P, Mermin J, Ryerson AB.
        JAMA Netw Open. 2018 Dec 7;1(8):e186371.

        Importance: Infection with hepatitis C virus (HCV) is a major cause of morbidity and mortality in the United States, and incidence has increased rapidly in recent years, likely owing to increased injection drug use. Current estimates of prevalence at the state level are needed to guide prevention and care efforts but are not available through existing disease surveillance systems. Objective: To estimate the prevalence of current HCV infection among adults in each US state and the District of Columbia during the years 2013 to 2016. Design, Setting, and Participants: This survey study used a statistical model to allocate nationally representative HCV prevalence from the National Health and Nutrition Examination Survey (NHANES) according to the spatial demographics and distributions of HCV mortality and narcotic overdose mortality in all National Vital Statistics System death records from 1999 to 2016. Additional literature review and analyses estimated state-level HCV infections among populations not included in the National Health and Nutrition Examination Survey sampling frame. Exposures: State, accounting for birth cohort, biological sex, race/ethnicity, federal poverty level, and year. Main Outcomes and Measures: State-level prevalence estimates of current HCV RNA. Results: In this study, the estimated national prevalence of HCV from 2013 to 2016 was 0.84% (95% CI, 0.75%-0.96%) among adults in the noninstitutionalized US population represented in the NHANES sampling frame, corresponding to 2035100 (95% CI, 1803600-2318000) persons with current infection; accounting for populations not included in NHANES, there were 231600 additional persons with HCV, adjusting prevalence to 0.93%. Nine states contained 51.9% of all persons living with HCV infection (California [318900], Texas [202500], Florida [151000], New York [116000], Pennsylvania [93900], Ohio [89600], Michigan [69100], Tennessee [69100], and North Carolina [66400]); 5 of these states were in Appalachia. Jurisdiction-level median (range) HCV RNA prevalence was 0.88% (0.45%-2.34%). Of 13 states in the western United States, 10 were above this median. Three of 10 states with the highest HCV prevalence were in Appalachia. Conclusions and Relevance: Using extensive national survey and vital statistics data from an 18-year period, this study found higher prevalence of HCV in the West and Appalachian states for 2013 to 2016 compared with other areas. These estimates can guide state prevention and treatment efforts.

      21. Healthcare utilization for common infectious disease syndromes in Soweto and Klerksdorp, South AfricaExternal
        Wong KK, von Mollendorf C, Martinson N, Norris S, Tempia S, Walaza S, Variava E, McMorrow ML, Madhi S, Cohen C, Cohen AL.
        Pan Afr Med J. 2018 ;30:271.

        Introduction: Understanding healthcare utilization helps characterize access to healthcare, identify barriers and improve surveillance data interpretation. We describe healthcare-seeking behaviors for common infectious syndromes and identify reasons for seeking care. Methods: We conducted a cross-sectional survey among residents in Soweto and Klerksdorp, South Africa. Households were interviewed about demographic characteristics; recent self-reported episodes of pneumonia, influenza-like illness (ILI), chronic febrile respiratory illness and meningitis in individuals of all ages; recent diarrhea in children aged < 5 years; and consultation with healthcare facilities and providers. Results: From July-October 2012, we interviewed 1,442 households in Klerksdorp and 973 households in Soweto. Public clinics were consulted most frequently for pneumonia, ILI and diarrhea in a child <5 years old at both sites; public hospitals were most frequently consulted for chronic respiratory and meningitis syndromes. Of all illness episodes reported, there were 110 (35%) in Klerksdorp and 127 (32%) in Soweto for which the person did not seek care with a licensed medical provider. Pharmacies were often consulted by individuals with pneumonia (Klerksdorp: 17, 16%; Soweto: 38, 22%) or ILI (Klerksdorp: 35, 24%; 44, 28%). Patients who did not seek care with a licensed provider reported insufficient time (Klerksdorp: 7%; Soweto, 20%) and lack of medications at the facility (Klerksdorp: 4%; Soweto: 8%) as barriers. Conclusion: Public government healthcare facilities are commonly consulted for infectious syndromes and pharmacies are frequently consulted particularly for respiratory diseases. Improving medication availability at healthcare facilities and streamlining healthcare delivery may improve access of licensed providers for serious illnesses.

    • Disaster Control and Emergency Services
      1. Determinants of oil-spill cleanup participation following the Deepwater Horizon oil spillExternal
        Sharpe JD, Kaufman JA, Goldman ZE, Wolkin A, Gribble MO.
        Environ Res. 2019 Jan 6;170:472-480.

        BACKGROUND: On April 20, 2010, the Deepwater Horizon oil rig exploded, spilling over 4.9 million barrels of oil in the Gulf of Mexico over an 87-day period and developing into a long-term environmental disaster that affected people living in Gulf Coast states. Engagement of community members in recovery efforts is important for mitigating adverse effects of disasters and accelerating the rebuilding process for impacted communities; however, few studies have explored factors that determine participation in oil spill cleanups. METHODS: We analyzed data from the Gulf States Population Survey (GSPS) to study the determinants of participating in the Deepwater Horizon Oil Spill cleanup. The GSPS was a random-digit dialing survey conducted on 38,361 adults in counties and parishes in Alabama, Florida, Louisiana, and Mississippi impacted by the oil spill. Using survey estimation to account for the complex survey design, we estimated the probability of cleanup participation and used logistic regression to examine the association between sociodemographic factors and cleanup participation. RESULTS: Approximately 4.7% of residents in affected Gulf communities participated in the cleanup. Most participants were young, men, non-Hispanic white, and employed. Living in an affected coastal county was associated with higher odds of participation (unadjusted odds ratio [OR]: 1.69; 95% confidence interval [CI]: 1.28-2.24), as was having excellent or very good physical health (OR: 2.05; 95% CI: 1.11-3.81). Older persons were less likely to participate in the cleanup (OR for 65+ age group vs. 18-24 age group: 0.14; 95% CI: 0.05-0.36). CONCLUSIONS: Understanding the demographics of cleanup participants may help inform civilian recruitment for future oil spill responses.

    • Drug Safety
      1. Trends in oral antibiotic prescription in dermatology, 2008 to 2016External
        Barbieri JS, Bhate K, Hartnett KP, Fleming-Dutra KE, Margolis DJ.
        JAMA Dermatol. 2019 Jan 16.

        Importance: Dermatologists prescribe more oral antibiotic courses per clinician than any other specialty, and this use puts patients at risk of antibiotic-resistant infections and antibiotic-associated adverse events. Objective: To characterize the temporal trends in the diagnoses most commonly associated with oral antibiotic prescription by dermatologists, as well as the duration of this use. Design, Setting, and Participants: Repeated cross-sectional analysis of antibiotic prescribing by dermatologists from January 1, 2008, to December 31, 2016. The setting was Optum Clinformatics Data Mart (Eden Prairie, Minnesota) deidentified commercial claims data. Participants were dermatology clinicians identified by their National Uniform Claim Committee taxonomy codes, and courses of oral antibiotics prescribed by these clinicians were identified by their National Drug Codes. Exposures: Claims for oral antibiotic prescriptions were consolidated into courses of therapy and associated with the primary diagnosis from the most recent visit. Courses were stratified into those of extended duration (>28 days) and those of short duration (</=28 days). Main Outcomes and Measures: Frequency of antibiotic prescribing and associated diagnoses. Poisson regression models were used to assess for changes in the frequency of antibiotic prescribing over time. Results: Between 2008 and 2016 among 985866 courses of oral antibiotics prescribed by 11986 unique dermatologists, overall antibiotic prescribing among dermatologists decreased 36.6% (1.23 courses per 100 visits) from 3.36 (95% CI, 3.34-3.38) to 2.13 (95% CI, 2.12-2.14) courses per 100 visits with a dermatologist (prevalence rate ratio for annual change, 0.931; 95% CI, 0.930-0.932), with much of this decrease occurring among extended courses for acne and rosacea. Oral antibiotic use associated with surgical visits increased 69.6% (2.73 courses per 100 visits) from 3.92 (95% CI, 3.83-4.01) to 6.65 (95% CI, 6.57-6.74) courses per 100 visits associated with a surgical visit (prevalence rate ratio, 1.061; 95% CI, 1.059-1.063). Conclusions and Relevance: Continuing to develop alternatives to oral antibiotics for noninfectious conditions, such as acne, can improve antibiotic stewardship and decrease complications from antibiotic use. In addition, the rising use of postoperative antibiotics after surgical visits is concerning and may put patients at unnecessary risk of adverse events. Future studies are needed to identify the value of this practice and the risk of adverse events.

    • Environmental Health
      1. Association of perfluoroalkyl and polyfluoroalkyl substances with adiposityExternal
        Cardenas A, Hauser R, Gold DR, Kleinman KP, Hivert MF, Fleisch AF, Lin PD, Calafat AM, Webster TF, Horton ES, Oken E.
        JAMA Netw Open. 2018 Aug 3;1(4):e181493.

        Importance: Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are ubiquitous synthetic chemicals that are suspected endocrine disruptors. Objectives: To determine the extent to which PFASs are associated with increases in weight and body size and evaluate whether a lifestyle intervention modifies this association. Design, Setting, and Participants: This prospective cohort study included 957 individuals who participated in the Diabetes Prevention Program trial, conducted from July 1996 to May 2001, and the Diabetes Prevention Program Outcomes Study, conducted from September 2002 to January 2014. Statistical analysis was conducted from September 1, 2017, to May 25, 2018. Interventions and Exposures: The initial lifestyle intervention consisted of training in diet, physical activity, and behavior modification, with the major goals of achieving 7% weight loss with subsequent maintenance and a minimum of 150 minutes per week of physical activity. Participants randomized to placebo received standard information about diet and exercise. A total of 6 plasma PFASs were quantified at baseline and 2 years after randomization, means were calculated from baseline and year 2 concentrations, and means were summed to assess total PFAS burden. Main Outcomes and Measures: Weight, waist circumference, and hip girth were measured at baseline and at scheduled visits. Results: Of the 957 participants, 625 (65.3%) were women and 731 participants (76.4%) were between 40 and 64 years of age; 481 participants were randomized to the lifestyle intervention and 476 participants were randomized to the placebo arm. The PFAS concentrations were not different by treatment arm and were similar to concentrations reported for the US population in 1999-2000. The association of PFAS and weight change differed by treatment. Each doubling in total PFAS concentration was associated with an increase of 1.80 kg (95% CI, 0.43-3.17 kg; P = .01) from baseline to 9 years after randomization for the placebo group but not the lifestyle intervention group (-0.59 kg; 95% CI, -1.80 to 0.62 kg; P = .34). Similarly, each doubling in PFAS was associated with a 1.03-cm increase in hip girth in the Diabetes Prevention Program trial for the placebo group (95% CI, 0.18-1.88 cm; P = .02) but not the lifestyle intervention group (-0.09 cm; 95% CI, -0.82 to 0.63 cm; P = .80). No associations were observed for changes in mean waist circumference. Conclusions and Relevance: Among adults at high risk for diabetes, higher plasma PFAS concentration was associated with increases in weight and hip girth over time, but a lifestyle intervention attenuated these associations. Diet and exercise may mitigate the obesogenic effects of environmental chemicals. Trial Registration: ClinicalTrials.gov Identifier: NCT00004992 and NCT00038727.

    • Genetics and Genomics
      1. Salmonella enterica serotype Lubbock emerged most likely from a Salmonella enterica serotype Mbandaka ancestor that acquired by recombination the fliC operon from Salmonella enterica serotype Montevideo. Here, we report the complete genome sequence of two S. Lubbock, one S. Montevideo, and one S. Mbandaka strain isolated from bovine lymph nodes.

      2. Genome sequences of penicillin-resistant Bacillus anthracis strainsExternal
        Gargis AS, Lascols C, McLaughlin HP, Conley AB, Hoffmaster AR, Sue D.
        Microbiol Resour Announc. 2019 Jan;8(2).

        Bacillus anthracis, the etiologic agent of anthrax, is characteristically susceptible to penicillin despite containing two chromosomal beta-lactamase genes. Few naturally occurring penicillin-resistant B. anthracis isolates have been reported. Here, we report the draft genome sequences for three penicillin-resistant B. anthracis strains, strain 32, UT308, and SK57.

    • Health Economics
      1. BACKGROUND: Treatment of non-communicable diseases (NCDs) in low-and-middle-income countries (LMICs) is costly and could expose households to financial hardship and vulnerability. This paper examines the association between medication costs of two major NCDs – hypertension (blood pressure) and diabetes, and household-level incidences of catastrophic health expenditure (CHE) in a South Asian LMIC, Pakistan. METHODS: The study analyzes self-reported blood pressure and diabetes (BPD) medication expenditure from the latest version (2015-16) of the Household Integrated Economic Survey (HIES) of Pakistan, a nationally representative survey of 24,238 households. The incidence of CHE is defined as households’ out-of-pocket (OOP) medical expenditure exceeding 10% of the total household expenditure. Using a linear probability model, we estimate the adjusted differences in CHE incidence between households that are spending and ‘not’ spending on BPD medication. We also analyze several hypothetical scenarios of BPD medication cost coverage, and compare the estimated CHE incidences of respective scenarios with the status quo. RESULTS: We find that the average monthly medical expenditure, and average medical expenditure share are significantly higher for households spending on BPD medication, compared to households ‘not’ spending. The incidence of CHE is found 6.7 percentage point higher for the households consuming BPD medication, after controlling for relevant socioeconomic attributes. If 25, 50, and 100% of the BPD medication OOP cost is covered, then the CHE incidence would reduce respectively by 5.9, 12.7, and 21.4% compared to the status quo. CONCLUSION: Medication cost for managing two major NCDs and household catastrophic health expenditure have strong associations. The findings inform policies toward ensuring access to necessary healthcare services, and protecting households from NCD treatment related financial hardship.

      2. Economic impact of malaria-related hospitalizations in the United States, 2000-2014External
        Khuu D, Eberhard ML, Bristow BN, Javanbakht M, Ash LR, Shafir SC, Sorvillo FJ.
        J Infect Public Health. 2019 Jan 7.

        BACKGROUND: Despite its elimination in the early 1950s, about 1700 cases of malaria are reported in the US every year. Few studies have quantified the direct and indirect costs of imported malaria in the US. METHODS: Disparities in the mean and total hospital days, hospital charges, and hospital costs for malaria-related hospitalizations in the US by demographic, clinical, species, financial, geographic, and institutional characteristics were examined using the 2000-2014 Nationwide Inpatient Sample (NIS). Trends and potential predictors for length of stay and hospital charges and costs were identified using negative binomial regression and linear regression, respectively. RESULTS: From 2000 to 2014, 22,029 malaria cases resulted in 95,948 hospital days for malaria-related hospitalizations, $176,391,466 in total hospital costs, and $555,435,849 in total charges. Mean charges increased significantly over the study period. Males, Blacks, and patients aged 25-44years accounted for the highest direct and indirect costs. Older age and having severe malaria was associated with a longer length of stay. Older age, severe malaria, HIV infection, and longer lengths of stay were associated with higher charges and costs. CONCLUSIONS: Malaria resulted in substantial direct and indirect costs in the US. Primary and secondary prevention measures should be prioritized among high-risk groups to reduce the economic burden.

    • Immunity and Immunization
      1. Effect of age at vaccination on rotavirus vaccine effectiveness in Bolivian infantsExternal
        Burke RM, Tate JE, Pringle KD, Patel M, De Oliveira LH, Parashar UD.
        Pediatr Infect Dis J. 2018 Aug;37(8):e216-e221.

        BACKGROUND: Rotavirus vaccines are less effective in developing countries versus developed countries. One hypothesis for this difference in performance is that higher levels of maternal antibodies in developing countries may interfere with vaccine response, suggesting that delayed dosing could be beneficial. The present analysis aims to assess whether rotavirus vaccine effectiveness (VE) varies by age at vaccination during routine use in Bolivia. METHODS: Data were merged from 2 postlicensure evaluations of monovalent rotavirus vaccine (RV1) in Bolivia, where 2 doses of RV1 are recommended at 2 and 4 months of age. For each dose, children were classified as receiving each dose “early,” “on-time” or “late.” Stratified unconditional logistic regression models were used to estimate VE, using unvaccinated children as the referent. VE was calculated as (1 – odds ratio) x 100%. Models were adjusted for hospital, age and time since RV1 introduction (via including terms for month and year of birth). RESULTS: VE for 2 doses of RV1 tended to be higher in infants receiving the first dose early (VE, 92%; 95% confidence interval: 70%-98%), when compared with infants receiving their first dose on-time [72% (62%-81%)] or late [68% (51%-79%)]. Estimates of VE were not substantially different when comparing children by age at second dose [early: VE, 76% (50%-89%); on-time: VE, 70% (50%-89%); late: VE, 75% (60%, 84%)], including all children. CONCLUSIONS: Our results indicate that early administration may improve VE and support the current World Health Organization recommendations for the RV1 schedule.

      2. BACKGROUND: The effectiveness of rotavirus vaccines in low and very low birth weight infants (LBW and VLBW) weighing <2500 and <1500 g at birth, respectively, a high-risk population for severe rotavirus gastroenteritis, has not been well examined. METHODS: We analyzed inpatient commercial claims data for US children <5 years of age from July 2001 to June 2015. Claims for acute gastroenteritis (AGE) and rotavirus-coded hospitalizations and LBW, VLBW and normal birth weight (NBW) infants were identified. Receipt of rotavirus vaccine was defined using Current Procedural Terminology. Rate reductions were calculated using prevaccine (2001-2006) and postvaccine (2007-2015) annual AGE and rotavirus hospitalization rates. RESULTS: As of December 2014, rotavirus vaccine coverage was 87%, 82% and 64%, for NBW, LBW and VLBW infants, respectively. For 2014-2015, among NBW, LBW and VLBW children <5 years of age, AGE hospitalization rate reductions relative to the prevaccine introduction period were 60% [95% confidence interval (CI): 58%-61%], 64% (95% CI: 57%-70%) and 55% (95% CI: 39%-67%), respectively. Rotavirus hospitalization rate reductions were 91% (95% CI: 90%-92%), 98% (95% CI: 93%-100%) and 93% (95% CI: 70%-98%). Rotavirus vaccines resulted in a 62% (95% CI: 51%-71%), 72% (95% CI: 44%-86%) and 71% (95% CI: 7%-91%) reduction in AGE hospitalization rates comparing vaccinated versus unvaccinated NBW, LBW and VLBW children 3-23 months of age, respectively. CONCLUSIONS: Rotavirus vaccines have substantially reduced AGE hospitalizations and are highly effective in LBW and VLBW infants, similar to NBW infants. Efforts to improve vaccination coverage, particularly in LBW and VLBW infants, should continue.

      3. Background: In July 2016, Sri Lanka replaced one intramuscular dose of inactivated poliovirus vaccine (IPV) with two doses of intradermal fractional IPV (fIPV) in its routine immunization schedule. We carried out a survey of seroprevalence of anti-polio antibodies in children who received two fIPV doses and compared it with those who received one full IPV dose. Methods: Children born between March and December 2016 were randomly selected from three Sri Lankan districts (Colombo, Badulla, Anuradhapura). Sera were collected and tested for presence of neutralizing antibodies to poliovirus types 1, 2, and 3. Results: Seroprevalence of anti-polio antibodies was 100% in all districts for poliovirus type 1 (PV1) and PV3; it ranged between 90-93% for PV2 in children who received one full IPV dose and between 78-100% in those receiving two fIPV doses (p=0.217). Median reciprocal titers of anti-PV2 antibodies were similar in those who received full IPV vs fIPV (1:64 vs 1:45 respectively; p=0.110). Interpretation: Our study demonstrated that Sri Lanka not only succeeded in maintaining very high primary immunization coverage but that it is feasible for a national immunization program to implement fIPV immunization and achieve high coverage with intradermal application. The seroprevalence of anti-PV2 antibodies did not decrease after the introduction of fIPV.

      4. Influenza vaccination coverage in children with neurologic disorders and their siblings, July 2006 to June 2014External
        Havers FP, Fry AM, Peacock G, Chen J, Reed C.
        Pediatr Infect Dis J. 2018 Aug;37(8):814-816.

        Children with neurologic disorders are at high risk for influenza-associated complications. We identified 184,460 children 1-17 years of age with neurologic disorders and 204,966 siblings in a commercial insurance claims database from July 2006 to June 2014. Among children with neurologic disorders, coverage increased from 22.4% in 2006-2007 to 42.3% in 2013-2014, but remained suboptimal. A lower proportion of siblings were vaccinated.

      5. Rapid behavioral assessment of barriers and opportunities to improve vaccination coverage among displaced Rohingyas in Bangladesh, January 2018External
        Jalloh MF, Bennett SD, Alam D, Kouta P, Lourenco D, Alamgir M, Feldstein LR, Ehlman DC, Abad N, Kapil N, Vandenent M, Conklin L, Wolff B.
        Vaccine. 2019 Jan 11.

        BACKGROUND: In November 2017, the World Health Organization received initial reports of suspected diphtheria cases in camps established for displaced Rohingyas in Cox’s Bazar district, Bangladesh. By January 11, 2018, over 4,000 suspected cases of diphtheria and 30 deaths were reported. The Bangladesh government and partners implemented a diphtheria vaccination campaign in December 2017. Outbreak response staff reported anecdotal evidence of vaccine hesitancy. Our assessment aimed to understand vaccination barriers and opportunities to enhance vaccine demand among displaced Rohingyas in Bangladesh. METHODS: In January 2018, we conducted a qualitative assessment consisting of nine focus group discussions and 15 key informant interviews with displaced Rohingyas in three camps. Participants included mothers and fathers with under five-year-old children, community volunteers, majhis (camp leaders), Islamic religious leaders, traditional and spiritual healers, and teachers. We recruited participants using purposive sampling, and analyzed the data thematically. RESULTS: Across focus groups and in-depth interviews, trusted information sources cited by participants included religious leaders, elders, village doctors, pharmacists, majhis, and mothers trained by non-governmental organizations to educate caregivers. Treatment of diphtheria and measles was usually sought from multiple sources including traditional and spiritual healers, village doctors, pharmacies, and health clinics. Major barriers to vaccination included: various beliefs about vaccination causing people to become Christian; concerns about multiple vaccines being received on the same day; worries about vaccination side effects; and, lack of sensitivity to cultural gender norms at the vaccination sites. CONCLUSION: Although vaccination was understood as an important intervention to prevent childhood diseases, participants reported numerous barriers to vaccination. Strengthening vaccine demand and acceptance among displaced Rohingyas can be enhanced by improving vaccination delivery practices and engaging trusted leaders to address religious and cultural barriers using community-based channels.

      6. Projected impact, cost-effectiveness, and budget implications of rotavirus vaccination in MongoliaExternal
        Lusvan ME, Debellut F, Clark A, Demberelsuren S, Otgonbayar D, Batjargal T, Purevsuren S, Groman D, Tate J, Pecenka C.
        Vaccine. 2019 Jan 10.

        INTRODUCTION: Rotavirus disease in Mongolia is estimated to cause more than 50 deaths yearly and many more cases and hospitalizations. Mongolia must self-finance new vaccines and does not automatically access Gavi prices for vaccines. Given the country’s limited resources for health, it is critical to assess potential new vaccine programs. This evaluation estimates the impact, cost-effectiveness, and budget implications associated with a nationwide rotavirus vaccine introduction targeting infants as part of the national immunization program in Mongolia, in order to inform decision-making around introduction. METHODS: The analysis examines the use of the two-dose vaccine ROTARIX(R), and three-dose vaccines ROTAVAC(R) and RotaTeq(R) compared to no vaccination from the government and the societal perspective. We use a modelling approach informed by local data and published literature to analyze the impact and cost-effectiveness of rotavirus vaccination over a ten-year time period starting in 2019, using a 3% discount rate. Our main outcome measure is the incremental cost-effectiveness ratio (ICER) expressed as US dollar per DALY averted. We assessed uncertainty around a series of parameters through univariate sensitivity analysis. RESULTS: Rotavirus vaccination in Mongolia could avert more than 95,000 rotavirus cases and 271 deaths, over 10years. Averted visits and hospitalizations represent US$2.4million in health care costs saved by the government. The vaccination program cost ranges from $6 to $11million depending on vaccine choice. From the governmental perspective, ICER ranged from $412 to $1050 and from $77 to $715 when considering the societal perspective. Sensitivity analysis highlights vaccine price as the main driver of uncertainty. CONCLUSION: Introduction of rotavirus vaccination is likely to be highly cost-effective in Mongolia, with ICERs estimated at only a fraction of Mongolia’s per capita GDP. From an economic standpoint, ROTAVAC(R) is the least costly and most cost-effective product choice.

      7. Anaphylaxis after vaccination reported to the Vaccine Adverse Event Reporting System, 1990-2016External
        Su JR, Moro PL, Ng C, Lewis PW, Said MA, Cano MV.
        J Allergy Clin Immunol. 2019 Jan 14.

        BACKGROUND: Anaphylaxis, a rare, potentially life-threatening hypersensitivity reaction, can occur after vaccination. OBJECTIVE: Describe reports of anaphylaxis after vaccination to the Vaccine Adverse Event Reporting System (VAERS) during 1990-2016. METHODS: We identified domestic reports of anaphylaxis within VAERS using a combination of Medical Dictionary for Regulatory Activity queries and Preferred Terms. We performed descriptive analysis, including history of hypersensitivity (e.g., anaphylaxis, respiratory allergies, drug allergies), and vaccines given. We reviewed all serious reports, and all non-serious reports with available medical records, to determine if they met the Brighton Collaboration case definition (BCCD) for anaphylaxis or were diagnosed by a physician. RESULTS: During the analytic period, VAERS received 467,960 total reports; 828 met BCCD for or were physician-diagnosed as anaphylaxis: 654 (79%) were classified as serious, and 669 (81%) had medical records available. Of 478 reports in children aged <19 years, 65% were male; childhood vaccines were most commonly reported. Of 350 reports in persons aged >/=19 years, 80% were female, and influenza vaccines were most frequently reported. Overall, 41% of reports described persons with no history of hypersensitivity. We identified 8 deaths, 4 among persons with no history of hypersensitivity. CONCLUSION: Anaphylaxis after vaccination is rare in the United States, and can occur among persons with no history of hypersensitivity. Most persons recover fully with treatment, but serious complications, including death, can occur.

      8. Development of a valid and reliable scale to assess parents’ beliefs and attitudes about childhood vaccines and their association with vaccination uptake and delay in GhanaExternal
        Wallace AS, Wannemuehler K, Bonsu G, Wardle M, Nyaku M, Amponsah-Achiano K, Dadzie JF, Sarpong FO, Orenstein WA, Rosenberg ES, Omer SB.
        Vaccine. 2019 Jan 11.

        BACKGROUND: Parents’ attitudes and beliefs in vaccination are important to understand for shaping vaccine acceptance and demand interventions. Little research has focused on developing a validated scale to measure parents’ attitudes towards vaccinations in low and middle-income countries; Ghana provided an opportunity develop a caregiver vaccination attitudes scale (CVAS) validated against childhood vaccine compliance. METHODS: We conducted a cluster survey of 373 households with children aged 12-35months of age from Northern Region, Ghana. Caregivers responded to 22 vaccination behavior and belief survey items and provided the child’s vaccination status. In exploratory factor analysis (EFA) to assess CVAS content validity, we used parallel analysis to guide the number of factors to extract and principal axis factor analysis for factor extraction. Reliability of the scale was assessed using McDonald’s Omega coefficient. Criterion validity of scale and subscales was assessed against receipt of vaccinations by 12months of age and vaccination delay, using number of days undervaccinated. RESULTS: EFA of CVAS responses resulted in removing 11 of 22 survey items due to loadings <0.30 and development of a 5-factor structure with subscales for Vaccine-Preventable Disease (VPD) Awareness, Vaccine Benefits, Past Behavior, Vaccine Efficacy and Safety, and Trust. The 5 factors accounted for 69% of the common variance and omega coefficients were >0.73 for all subscales. Validity analysis indicated that for every unit increase in the parent’s scale score, the odds of the child being vaccinated decreased by 0.58 (95% confidence interval [CI]: 0.37, 0.68) and the number of days under-vaccinated increased by 86 (95%CI: 28, 143). The final 3-factor scale included Vaccine Benefits, Past Behavior, and Vaccine Efficacy and Safety. DISCUSSION: The final CVAS included three factors associated with vaccine compliance in Ghana, although several survey items suggested for use in vaccine acceptance scales were dropped. Replicating this study in several country settings will provide additional evidence to assist in refining a tool for use in routine vaccine acceptance and demand surveillance efforts.

    • Injury and Violence
      1. Characteristics of animal-related motor vehicle crashes in select National Park Service units – United States, 1990-2013External
        Cherry CC, Dietz S, Sauber-Schatz E, Russell S, Proctor J, Buttke D.
        Traffic Inj Prev. 2019 Jan 15:1-6.

        OBJECTIVES: Nationally, animal-motor vehicle crashes (AVCs) account for 4.4% of all types of motor vehicle crashes (MVCs). AVCs are a safety risk for drivers and animals and many National Park Service (NPS) units (e.g., national park, national monument, or national parkway) have known AVC risk factors, including rural locations and substantial animal densities. We sought to describe conditions and circumstances involving AVCs to guide traffic and wildlife management for prevention of AVCs in select NPS units. METHODS: We conducted an analysis using NPS law enforcement MVC data. An MVC is a collision involving an in-transit motor vehicle that occurred or began on a public roadway. An AVC is characterized as a collision between a motor vehicle and an animal. A non-AVC is a crash between a motor vehicle and any object other than an animal or noncollision event (e.g., rollover crash). The final data for analysis included 54,068 records from 51 NPS units during 1990-2013. Counts and proportions were calculated for categorical variables and medians and ranges were calculated for continuous variables. We used Pearson’s chi-square to compare circumstances of AVCs and non-AVCs. Data were compiled at the park regional level; NPS parks are assigned to 1 of 7 regions based on the park’s location. RESULTS: AVCs accounted for 10.4% (5,643 of 54,068) of all MVCs from 51 NPS units. The Northeast (2,021 of 5,643; 35.8%) and Intermountain (1,180 of 5,643; 20.9%) regions had the largest percentage of the total AVC burden. November was the peak month for AVCs across all regions (881 of 5,643; 15.6%); however, seasonality varied by park geographic regions. The highest counts of AVCs were reported during fall for the National Capital, Northeast/Southeast, and Northeast regions; winter for the Southeast region; and summer for Intermountain and Pacific West regions. CONCLUSIONS: AVCs represent a public health and wildlife safety concern for NPS units. AVCs in select NPS units were approximately 2-fold higher than the national percentage for AVCs. The peak season for AVCs varied by NPS region. Knowledge of region-specific seasonality patterns for AVCs can help NPS staff develop mitigation strategies for use primarily during peak AVC months. Improving AVC data collection might provide NPS with a more complete understanding of risk factors and seasonal trends for specific NPS units. By collecting information concerning the animal species hit, park managers can better understand the impacts of AVC to wildlife population health.

      2. Effect of a behavioral intervention on perpetrating and experiencing forced sex among South African adolescents: A secondary analysis of a cluster randomized trialExternal
        Jemmott JB, O’Leary A, Jemmott LS, Ngwane ZP, Teitelman AM, Makiwane MB, Bellamy SL.
        JAMA Netw Open. 2018 Aug 3;1(4):e181213.

        Importance: Scant research has investigated interventions to reduce forced sexual intercourse among adolescents. The need for such interventions is especially great in South Africa, which has some of the highest rates of sexual assault in the world. Objectives: To determine whether an HIV/sexually transmitted disease risk-reduction intervention that reduced sexual risk behavior and sexually transmitted disease prevalence also reduced the perpetration and experience of forced sex among South African adolescents. Design, Setting, and Participants: A cluster randomized clinical trial, at schools located in a township and a semirural area, Eastern Cape Province, South Africa. Matched pairs of schools were randomly selected (9 of 17); of 1118 students in sixth grade at these 18 schools who had parent or guardian consent, 1057 (94%) were enrolled, and those not reporting forced sex perpetration before the intervention were included in the analyses (n = 1052). Post hoc secondary analysis of a cluster randomized clinical trial was performed, with baseline and 3-, 6-, 12-, 42-, and 54-month postintervention assessments between October 4, 2004, and June 30, 2010. Generalized estimating equation Poisson regression analyses adjusting for gender and clustering within schools were conducted between August 23, 2017, and April 30, 2018. Recruiters and data collectors, but not intervention facilitators, were blind to the participants’ intervention assignment. Interventions: Theory-based, culturally adapted, 6-session HIV/sexually transmitted disease risk-reduction intervention (Let Us Protect Our Future intervention) and attention-matched, chronic disease prevention control intervention implemented by specially trained man and woman cofacilitators from the community. Main Outcomes and Measures: Study outcomes for this secondary analysis (planned after the data were collected) are self-reports of perpetrating and experiencing forced vaginal intercourse. Results: Participants included 1052 adolescents (557 girls [53%]; mean [SD] age, 12.4 [1.2] years) reporting not perpetrating forced sex at baseline. Fewer intervention than control participants reported forced sex perpetration postintervention compared with the control group at 3 months (9 of 561 [2%] vs 20 of 491 [4%]; risk ratio [RR], 0.978; 95% CI, 0.959-0.997), 6 months (17 of 561 [3%] vs 35 of 491 [7%]; RR, 0.964; 95% CI, 0.941-0.988), 12 months (21 of 561 [4%] vs 42 of 491 [9%]; RR, 0.959; 95% CI, 0.934-0.985), 42 months (41 of 561 [7%] vs 56 of 491 [11%]; RR, 0.967; 95% CI, 0.937-0.998), and 54 months (52 of 561 [9%] vs 68 of 491 [14%]; RR, 0.964; 95% CI, 0.932-0.997). Conclusions and Relevance: In settings with high rates of sexual assault, the use of theory-based culturally adapted interventions with early adolescents may reduce rates of perpetrating and experiencing forced sex. Trial Registration: ClinicalTrials.gov Identifier: NCT00559403.

      3. Commonalities and differences in social norms related to corporal punishment among black, Latino and white parentsExternal
        Klevens J, Mercer Kollar L, Rizzo G, O?Shea G, Nguyen J, Roby S.
        Child Adolesc Social Work J. 2019 .

        To establish commonalities and differences in social norms related to corporal punishment among Black, Latino, and White parents, we first examine survey data from a random sample of a nationally representative opt-in internet panel (n = 2500) to establish the frequency of corporal punishment among parents of children under five (n = 540) and their perceptions of the frequency of use of corporal punishment in their community and whether they ought to use corporal punishment. We disaggregate by race/ethnicity and education to identify higher risk groups. To better understand the beliefs underlying these perceptions among the higher risk group (i.e., less educated), we used a grounded theory approach to analyze data from 13 focus groups (n = 75) segmented by race/ethnicity (i.e., Black, Latino, or White), gender (i.e., mothers or fathers), and population density (i.e., rural or urban). Survey findings revealed that 63% of parents spanked, albeit the majority seldom or sometimes. Spanking was most frequent among Latinos (73%) and lowest among White parents (59%). While all participants across racial/ethnic groups believed the majority of parents spanked, even more than the proportion that actually do, about half believed they ought to spank. Perceptions of the frequency and acceptability of corporal punishment were associated with use of corporal punishment. The qualitative findings highlight more similarities than differences across Black, Latino, and White communities. The findings suggest social norms change efforts might focus on parents with less education and influencing perceptions around whether they ought to spank.

      4. PURPOSE: The aim was to assess the associations of antibullying U.S. state statutes that enumerate sexual orientation with exposure to bullying and other stressors and with suicidal ideation and suicide attempts in sexual minority and non sexual minority youth. METHODS: We analyzed data from the 2015 national school-based Youth Risk Behavior Survey, representative of 9th through 12th grade students attending public and private schools in the United States. We reviewed each state’s antibullying statutes and classified them on enumeration. RESULTS: Antibullying state laws that enumerate sexual orientation were associated with lower risk for suicide attempts and serious attempts requiring medical attention and lower risk for forced sexual intercourse. They were also associated with feeling safe at school or on the way to or from school. Results did not differ by sexual orientation. CONCLUSIONS: Enumeration of sexual orientation was associated with reduced stressors and suicide attempts, but it is insufficient to remove significant disparities based on sexual orientation. Additional policies and practices are required to address persistent sexual orientation disparities in exposure to bullying and suicidal behavior.

    • Laboratory Sciences
      1. Antenatal and intrapartum nucleic acid amplification test use for group B Streptococcus screening – United States, 2016External
        Fay K, Almendares O, Robinson-Dunn B, Schrag S.
        Diagn Microbiol Infect Dis. 2018 Dec 11.

        Perinatal group B Streptococcus (GBS) disease prevention guidelines in 2010 allowed for processing of screening specimens by nucleic acid amplification tests (NAATs); however, the extent of NAAT use is unknown. A 2016 laboratory survey sent to 10 surveillance sites found that 18.7% of responding laboratories offered NAAT for GBS screening (antenatal only: 7.3%; intrapartum only: 4.1%; both: 3.4%).

      2. BACKGROUND: Dried blood spots (DBS), collected universally from newborns in the U.S., could be used as a matrix for the detection of cytomegalovirus (CMV) infection in infants. However, sensitivity to detect CMV in DBS as compared to saliva and urine is variable across studies largely due to the DNA extraction method. Thermal shock, a widely used DNA extraction method, is highly sensitive for the detection of CMV in DBS, however, the processing time required is not practical for high-throughput testing. OBJECTIVE: To determine if rapid and cost-effective DNA extraction methods amenable to newborn screening (NBS) could achieve the same sensitivity as the thermal shock method. STUDY DESIGN: DBS were prepared from CMV positive blood samples from 20 organ transplant recipients. Three DNA extraction methods were compared for relative yield and sensitivity of detection of CMV DNA: thermal shock, KOH Tris buffer, and DNA Extract All. CMV DNA was detected by real-time quantitative polymerase chain reaction (qPCR). RESULTS: The KOH Tris and DNA Extract All methods gave higher yields and sensitivity of CMV detection in DBS than thermal shock, which were significantly greater when viral loads were </= 10,000 copies/ml blood. Both methods gave faster turnaround times than thermal shock and would be better suited for NBS. CONCLUSIONS: The choice of DNA extraction method greatly influences the ability to detect low levels of CMV DNA in DBS. Moreover, development of highly sensitive yet rapid methods for CMV detection could help facilitate future newborn screening of CMV in DBS.

      3. Evaluation of five rapid diagnostic tests for detection of antibodies to hepatitis C virus (HCV): A step towards scale-up of HCV screening efforts in IndiaExternal
        Mane A, Sacks J, Sharma S, Singh H, Tejada-Strop A, Kamili S, Kacholia K, Gautam R, Thakar M, Gupta RS, Gangakhedkar R.
        PLoS One. 2019 ;14(1):e0210556.

        OBJECTIVES: Hepatitis C virus (HCV) infection is a major contributor to morbidity and mortality worldwide. Early detection and curative treatment of HCV can reduce the risk of liver-related mortality and serve to prevent transmission of new infections. India is estimated to have about six million HCV infected individuals, most of whom are unaware of their infection status. Rapid diagnostic test kits (RDTs) could help identify HCV infected persons more expeditiously and thus availability of high performing, quality-assured RDTs is essential to scale-up HCV screening efforts. The present study was thus undertaken to evaluate the performance characteristics of five anti-HCV RDTs. METHODS: Five anti-HCV RDTs (Alere Truline, Flaviscreen, Advanced Quality, SD Bioline and OraQuick) were evaluated using two panels of known anti-HCV positive and negative samples; one characterized from Indian patient samples (n = 360) and other obtained from the US Centers for Disease Control and Prevention (CDC), Atlanta (n = 100). Sensitivity, specificity, inter-observer agreement, test validity and operational characteristics of RDTs were assessed. RESULTS: The combined sensitivities across both panels for Alere Truline, Flaviscreen, Advanced Quality, SD Bioline and OraQuick RDTs were 99.4% (95%CI-96.6%-99.9%), 86.2% (95%CI-79.8%-91.1%), 96.2% (95%CI-91.9%-98.6%), 99.4% (95%CI-96.6%-99.9%) and 99.4% (95%CI-96.6%-99.9%) respectively. The overall specificities across both panels for all RDTs were 99.7%. The inter-observer agreement was 100% for Alere Truline, SD Bioline and OraQuick, while it was 99.5% and 98.6% with Advanced Quality and Flavicheck respectively. Discordant results were significantly associated with human immunodeficiency virus (HIV) positivity for both Advanced Quality and Flavicheck (p<0.001). CONCLUSION: The present evaluation demonstrated that Alere Truline, SD Bioline and OraQuick RDTs had sensitivity and specificity in accordance with the acceptance criteria of the Drug Controller General, India, the national regulatory authority, had excellent inter-observer agreement and superior operational characteristics. Our findings suggest that certain HCV RDTs perform well and can be a useful tool in screening of HCV infections expeditiously.

      4. Comparison of multi-wall carbon nanotube and nitrogen-doped multi-wall carbon nanotube effects on lung function and airway reactivity in ratsExternal
        Russ KA, Thompson JA, Kashon M, Porter DW, Friend SA, McKinney W, Fedan JS.
        Toxicol Appl Pharmacol. 2019 Feb 1;364:153-163.

        Incorporation of multi-wall carbon nanotubes (MWCNT) into materials has raised concerns about their potential hazards to manufacturing workers. In animal models, airway inflammation and lung fibrosis follow aspiration, instillation, and inhalation exposures to MWCNT. However, the effects of MWCNT on pulmonary function, airway reactivity and airway epithelium function following inhalation exposure has not been studied. We investigated whether inhaled MWCNT affects lung resistance (RL) and dynamic compliance (Cdyn), reactivity to inhaled methacholine (MCh), epithelial regulation of airway reactivity to MCh in vitro, and airway epithelial ion transport. Male rats were exposed by whole body inhalation for 6h to air or aerosolized MWCNT (0.5, 1 or 5mg/m(3)) for one or nine days. Eighteen h after 1 d exposure to 5mg/m(3) MWCNT, basal RL was increased and basal Cdyn was decreased; changes did not persist for 7 d. Reactivity to MCh (RL) was increased and Cdyn responses were decreased at 18h, but not 7 d after exposure to 1 and 5mg/m(3) MWCNT. The effects of i.t.-instilled MWCNT and nitrogen-doped MWCNT (N-MWCNT) on pulmonary function and reactivity to MCh at doses comparable to deposition after inhalation of 5mg/m(3) at 1 d and 0.5, 1, and 5mg/m(3) MWCNT 9 d-exposures were compared. Both nanoparticles increased airway reactivity (RL); N-MWCNT did not affect Cdyn responses. Lung function and airway reactivity are altered following a single MWCNT inhalation and generally subside over time. Given i.t., MWCNT’s and N-MWCNT’s effects were comparable, but N-MWCNT evoke smaller changes in Cdyn responses.

      5. Diagnosis of parasitic diseases that involve tissue-stage larvae is challenging, and serology remains the most effective antemortem test for detecting these infections. Baylisascaris procyonis, the raccoon roundworm, is a zoonotic ascarid. Raccoons are the usual definitive host, and humans may be infected as accidental hosts. More than 150 species of birds and mammals may act as paratenic hosts, and rodents play an important role in the transmission and maintenance of this parasite in nature. Migratory larvae in paratenic host tissues can produce ocular disease and severe to fatal neurologic disease, but not all infected hosts develop signs. A sensitive and specific Western blot (WB) assay based on a recombinant Baylisascaris-specific antigen (rBpRAG-1) has been developed for use in humans. We evaluated the use of this antigen to detect Baylisascaris spp. infections in rodent paratenic hosts. With the use of 4 species of Peromyscus mice ( Peromyscus californicus, Peromyscus leucopus, Peromyscus maniculatus, Peromyscus polionotus) from a previous infection trial, we developed species-adapted WB and ELISA assays and evaluated performance compared to detection of larvae in tissue samples. These assays revealed species-level differences in seroconversion and terminal antibody concentrations, with P. leucopus developing significantly greater antibody concentrations than P. californicus and P. polionotus at all dose levels, and P. maniculatus at the low dose. Some P. californicus and P. polionotus failed to seroconvert despite the recovery of larvae from their tissues. WB and ELISA results were correlated; however, the WB demonstrated higher sensitivity than the ELISA overall (72.2% versus 63.9%, respectively). With the use of experimental samples, specificity was 100% for WB and 94.1% for ELISA. A WB was also used to test Mus and Rattus samples, and although numbers were too limited to evaluate sensitivity and specificity, all animals known to be infected by tissue digestion were WB positive, and all uninfected animals were negative. Finally, the Peromyscus-adapted WB and ELISA were used to test a set of serum samples from wild-trapped P. maniculatus and Rattus rattus. Both assays were generally sensitive, but specificity was equivocal. This emphasizes the challenge of using serology for investigation of wildlife diseases, in which hosts have unknown exposure histories. Nevertheless, serologic methods have utility in the study of Baylisascaris spp. in paratenic hosts, either wild or captive, and have advantageous attributes (non-lethal, high-throughput), but results should be interpreted carefully.

      6. Didecyldimethylammonium chloride (DDAC) is an antimicrobial dialkyl-quaternary ammonium compound used in industrial and commercial products. Clinical data suggest that DDAC exposure elicits multiple types of hypersensitivity reactions; here, we confirm this observation in a BALB/c murine model. To examine the immunological mechanism behind this mixed-type response and the potential involvement of type 2 innate lymphoid cells (ILC2s), we assessed early immune responses in the skin following topical DDAC exposure (0.125% and 0.5%). DDAC exposure resulted in a rapid and dramatic increase in the Th2-skewing and ILC2 activating cytokine thymic stromal lymphopoietin. Correspondingly, dermal ILC2s were activated 24 hours after DDAC exposure, resulting in increased expression of CD25, ICOS and KLRG1, and decreased CD127 throughout 7 days of exposure. Following ILC2 activation, the Th2 cytokine IL-4 was elevated compared to control mice in total ear protein lysate (0.5% DDAC). Rag2-/- mice were used to determine a functional role for ILC2s in DDAC induced sensitization. ILC2s from Rag2-/- mice were similarly activated by DDAC and, importantly, produced significant levels of IL-4 and IL-5 in the skin (0.5% DDAC). These data indicate that ILC2s contribute to early Th2 immune responses following DDAC exposure. ILC2s have been previously implicated in allergic responses, but to our knowledge have not been thoroughly investigated in chemical sensitization. These results indicate that following DDAC exposure, skin ILC2s become activated and produce Th2 cytokines, providing a possible mechanism for the development of the mixed-type allergic responses commonly observed with chemical sensitizers.

    • Maternal and Child Health
      1. Gastroschisis trends and ecologic link to opioid prescription rates – United States, 2006-2015External
        Short TD, Stallings EB, Isenburg J, O’Leary LA, Yazdy MM, Bohm MK, Ethen M, Chen X, Tran T, Fox DJ, Fornoff J, Forestieri N, Ferrell E, Ramirez GM, Kim J, Shi J, Cho SJ, Duckett K, Nelson N, Zielke K, St John K, Martin B, Clark C, Huynh MP, Benusa C, Reefhuis J.
        MMWR Morb Mortal Wkly Rep. 2019 Jan 18;68(2):31-36.

        Prevalence of gastroschisis, a serious birth defect of the abdominal wall resulting in some of the abdominal contents extending outside the body at birth, has been increasing worldwide (1,2). Gastroschisis requires surgical repair after birth and is associated with digestive and feeding complications during infancy, which can affect development. Recent data from 14 U.S. states indicated an increasing prevalence of gastroschisis from 1995 to 2012 (1). Young maternal age has been strongly associated with gastroschisis, but research suggests that risk factors such as smoking, genitourinary infections, and prescription opioid use also might be associated (3-5). Data from 20 population-based state surveillance programs were pooled and analyzed to assess age-specific gastroschisis prevalence during two 5-year periods, 2006-2010 and 2011-2015, and an ecologic approach was used to compare annual gastroschisis prevalence by annual opioid prescription rate categories. Gastroschisis prevalence increased only slightly (10%) from 2006-2010 to 2011-2015 (prevalence ratio = 1.1, 95% confidence interval [CI] = 1.0-1.1), with the highest prevalence among mothers aged <20 years. During 2006-2015, the prevalence of gastroschisis was 1.6 times higher in counties with high opioid prescription rates (5.1 per 10,000 live births; CI = 4.9-5.3) and 1.4 times higher where opioid prescription rates were medium (4.6 per 10,000 live births; CI = 4.4-4.8) compared with areas with low prescription rates (3.2 per 10,000 live births; CI = 3.1-3.4). Public health research is needed to understand factors contributing to the association between young maternal age and gastroschisis and assess the effect of prescription opioid use during pregnancy on this pregnancy outcome.

    • Occupational Safety and Health
      1. Trust in the work environment and cardiovascular disease risk: Findings from the Gallup-Sharecare Well-Being IndexExternal
        Alterman T, Tsai R, Ju J, Kelly KM.
        Int J Environ Res Public Health. 2019 Jan 15;16(2).

        This study examined associations between trust, an important aspect of workplace social capital, with seven cardiovascular disease (CVD) risk factors (American Heart Association Life’s Simple 7 (LS7)): smoking, obesity, low physical activity, poor diet, diabetes, high cholesterol, and high blood pressure. Data are from the U.S. Gallup-Sharecare Well-Being Index (2010(-)2012), a nationally representative telephone survey of U.S. workers (n = 412,884). The independent variable was the response to a work environment (WE) question as to whether their supervisor always creates an open and trusting environment. Regression models were adjusted for demographic characteristics with each of the LS7 CVD risk factors as dependent variables. Twenty-one percent of workers reported that their supervisor did not create an open and trusting environment. Trust was associated with increased adjusted odds of having many of the LS7 CVD risk factors. Among those workers whose supervisor created a mistrustful environment, the odds ratios were greatest (>20%) for having four or more of the LS7 CVD risk factors.

      2. Endotoxin exposures during harvesting and processing cannabis at an outdoor cannabis farmExternal
        Couch JR, Burton NC, Victory KR, Green BJ, Lemons AR, Nayak AP, Beezhold DH.
        Aerobiologia. 2019 .

        Legalization of medicinal and recreational cannabis use in numerous states within the USA has resulted in the increased commercial cultivation of cannabis. Outdoor cannabis farming operations present a variety of potential physical, chemical, and biological hazards that currently remain uncharacterized. Worker exposures to endotoxins were evaluated at an outdoor US cannabis farm during harvesting and processing activities. Endotoxin area air sample concentrations ranged from below the limit of detection to 15 endotoxin units per cubic meter (EU/m3). Endotoxin breathing zone measurements (2.8?37 EU/m3) were below the Dutch Expert Committee on Occupational Safety occupational exposure limit of 90 /m3. During confidential medical interviews, no adverse health effects were reported by workers while harvesting or processing cannabis. Further endotoxin exposure assessments should be performed especially in larger, indoor cannabis operations where a confined environment may result in higher endotoxin exposures than observed in this outdoor environment.

      3. Shift work and biomarkers of subclinical cardiovascular disease: The BCOPS StudyExternal
        Holst MM, Wirth MD, Mnatsakanova A, Burch JB, Charles LE, Tinney-Zara C, Fekedulegn D, Andrew ME, Hartley TA, Violanti JM.
        J Occup Environ Med. 2019 Jan 9.

        OBJECTIVE: To assess the association of shift work with biomarkers of subclinical cardiovascular disease and examine the moderating role of body mass index (BMI) in a police cohort METHODS: A cross-sectional analysis was conducted among officers who were categorized as working the day, evening, or night shift. Comparisons with inflammatory biomarkers were performed among shifts using analysis of variance/covariance and further stratified by BMI to assess potential effect modification. RESULTS: Associations were observed between day and night shift workers for leukocytes, tumor necrosis factor alpha and homocysteine. After BMI stratification, higher c-reactive protein (CRP) levels were observed among evening shift workers with a BMI >/= 30 kg/m. versus the day shift. CONCLUSIONS: Future studies examining prospective changes in these markers will allow for more comprehensive evaluation of their association with shift work.

      4. Performance evaluation of disposable inhalable aerosol sampler at a copper electrorefineryExternal
        Lee EG, Grimson PJ, Chisholm WP, Kashon ML, He X, L’Orange C, Volckens J.
        J Occup Environ Hyg. 2019 Jan 14:1-10.

        This study evaluates the performance of the disposable inhalable aerosol sampler (DIAS), a new sampler developed to be more cost-effective than the traditional inhalable particle samplers and comparable to the inhalable particle sampling convention. Forty-eight pairs of the DIAS prototype and the IOM sampler were utilized to collect copper exposure measurements (23 personal and 25 area) at an electrorefinery facility. The geometric mean (GM) value of ratios of exposure data (DIAS/IOM) was 1.1, while the GM of ratios (DIAS/IOM) was 1.6 for the area exposure data, revealing 84%of the ratios were greater than one. For both personal and area exposure data, the concordance correlation coefficient tests revealed significant disagreements between the two types of samplers and suggested precision as the source of the disagreement. The estimated mean concentration was higher for the DIAS compared that for the IOM for the area exposure data (p < 0.05), while the results were comparable for the personal exposure data (p = 0.49). Overall, the DIAS generated higher exposure results compared to the IOM sampler for the area exposures. For the personal exposures, the findings were inconclusive due to inconsistent results of factors aforementioned. This study is limited to one metal component (copper) of the dust at a worksite. To date, this is the first field evaluation using personal exposure data to test the performance of the DIAS and the second evaluation using area exposure data. Thus, it will be necessary to conduct additional field evaluations with various elements to further evaluate the performance of the DIAS. In addition, particle migration to the internal walls of the cap was observed during the transportation of collected samples to a laboratory for both sampler types (6.4% for the DIAS and 7.4% for the IOM). Occupational health and safety professionals should be aware of potential errors caused from transferring samples from a field to a laboratory and should be careful not to exclude particles collected on the caps.

      5. Using trunk posture to monitor heat strain at workExternal
        Quinn TD, Seo Y, Yorio PL, Aljaroudi A, Coca A, Kim J, Roberge RJ, Williams WJ.
        Ergonomics. 2018 :1-9.

        AbstractThis study aimed to determine if trunk posture during walking is related to increases in rectal temperature (Tre). 24 males treadmill walked in one of four conditions (1): 30 min at 3.0 mph and 0% grade, 20C and 50% relative humidity (RH), wearing healthcare worker (HCW) PPE; (2): 30 min at 3.0 mph and 0% grade, 27.5C and 60% RH, HCW PPE; (3): 30 min at 3.0 mph and 0% grade, 32.5C and 70% RH, HCW PPE; and (4): 40 min at 40% VO2max, 30C and 70% RH, wearing firefighter PPE. Trunk posture (Zephyr BioHarness 3) and Tre were measured continuously. Tre was positively related to trunk posture, controlling for covariates (B=3.49, p<.001). BMI and age moderated this relationship (Tre age, B = 0.76, p<.001; Tre*BMI, B=1.85, p<.001). Trunk posture measurement may be useful in monitoring fall potential and magnitude of heat stress of workers in hot environments.Practitioner Summary: Occupational hyperthermia increases worker risk for heat illness and injury but is difficult to monitor in the field. This investigation shows that trunk posture is independently and positively related to core temperature. Non-invasive measurement or visual inspection of trunk posture could provide novel insight on individual heat strain level.

      6. Objectives The widespread application of nano-enabled products and the increasing likelihood for workplace exposures make understanding engineered nanomaterial (ENM) effects in exposed workers a public and occupational health priority. The aim of this study was to report on the current state of knowledge on possible adverse effects induced by ENM in humans to determine the toxicological profile of each type of ENM and potential biomarkers for early detection of such effects in workers. Methods A systematic review of human studies and epidemiological investigations of exposed workers relative to the possible adverse effects for the most widely used ENM was performed through searches of major scientific databases including Web of Science, Scopus, and PubMed. Results Twenty-seven studies were identified. Most of the epidemiological investigations were cross-sectional. The review found limited evidence of adverse effects in workers exposed to the most commonly used ENM. However, some biological alterations are suggestive for possible adverse impacts. The primary targets of some ENM exposures were the respiratory and cardiovascular systems. Changes in biomarker levels compared with controls were also observed; however, limited exposure data and the relatively short period since the first exposure may have influenced the incidence of adverse effects found in epidemiological studies. Conclusions There is a need for longitudinal epidemiologic investigations with clear exposure characterizations for various ENM to discover potential adverse health effects and identify possible indicators of early biological alterations. In this state of uncertainty, precautionary controls for each ENM are warranted while further study of potential health effects continues.

    • Parasitic Diseases
      1. Malaria vaccine trials in pregnant women: An imperative without precedentExternal
        Healy SA, Fried M, Richie T, Bok K, Little M, August A, Riley L, Swamy GK, Wylie BJ, Menendez C, Muehlenbachs A, Doumbo O, Greenwood B, Billingsley PF, Hoffman SL, Duffy PE.
        Vaccine. 2019 Jan 6.

        Pregnant women are highly susceptible to Plasmodium falciparum malaria, leading to substantial maternal, perinatal, and infant mortality. While malaria vaccine development has made significant progress in recent years, no trials of malaria vaccines have ever been conducted in pregnant women. In December 2016, an expert meeting was convened at NIAID, NIH, in Rockville, Maryland to deliberate on the rationale and design of malaria vaccine trials in pregnant women. The discussions highlighted the progress made over recent years in the field of maternal immunization for other infectious diseases, and the evolving regulatory and ethical environment, all of which support a new emphasis on testing malaria vaccines that offer direct benefits to pregnant women. Initial safety and immunogenicity studies of malaria vaccines will be conducted in non-pregnant adult volunteers. Subsequently, efficacy trials involving pregnant women will likely be conducted in malaria-endemic and often resource-poor environments where sufficiently high malaria incidence will allow vaccine activity to be measured. Such trials will need to meet all international standards to ensure the safety of mother and offspring, under oversight of appropriate ethical and regulatory bodies. The convened experts drafted a clinical development plan to test a malaria vaccine product during pregnancy, using as a case study PfSPZ Vaccine being developed by Sanaria Inc. that is currently in phase 2 testing. Following the expert recommendations, a pregnancy registry has been initiated in Ouelessebougou, Mali, to provide baseline information on maternal and fetal outcomes as a context for evaluating PfSPZ Vaccine safety in the future, and new regimens are being assessed that will be suitable for evaluation in pregnant women.

    • Physical Activity
      1. Developing core capabilities for local health departments to engage in land use and transportation decision making for active transportationExternal
        Lemon SC, Goins KV, Sreedhara M, Arcaya M, Aytur SA, Heinrich K, Kerner B, Lyn R, Maddock JE, Riessman R, Schmid TL.
        J Public Health Manag Pract. 2019 Jan 8.

        OBJECTIVE: To develop a core set of capabilities and tasks for local health departments (LHDs) to engage in land use and transportation policy processes that promote active transportation. DESIGN: We conducted a 3-phase modified Delphi study from 2015 to 2017. SETTING: We recruited a multidisciplinary national expert panel for key informant interviews by telephone and completion of a 2-step online validation process. PARTICIPANTS: The panel consisted of 58 individuals with expertise in local transportation and policy processes, as well as experience in cross-sector collaboration with public health. Participants represented the disciplines of land use planning, transportation/public works, public health, municipal administration, and active transportation advocacy at the state and local levels. MAIN OUTCOME MEASURES: Key informant interviews elicited initial capabilities and tasks. An online survey solicited rankings of impact and feasibility for capabilities and ratings of importance for associated tasks. Feasibility rankings were used to categorize capabilities according to required resources. Results were presented via second online survey for final input. RESULTS: Ten capabilities were categorized according to required resources. Fewest resources were as follows: (1) collaborate with public officials; (2) serve on land use or transportation board; and (3) review plans, policies, and projects. Moderate resources were as follows: (4) outreach to the community; (5) educate policy makers; (6) participate in plan and policy development; and (7) participate in project development and design review. Most resources were as follows: (8) participate in data and assessment activities; (9) fund dedicated staffing; and (10) provide funding support. CONCLUSIONS: These actionable capabilities can guide planning efforts for LHDs of all resource levels.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

    • Public Health Leadership and Management
      1. Success of a South-South collaboration on Human Resources Information Systems (HRIS) in health: a case of Kenya and Zambia HRIS collaborationExternal
        Were V, Jere E, Lanyo K, Mburu G, Kiriinya R, Waudo A, Chiteba B, Waters K, Mehta P, Oluoch T, Rodgers M.
        Hum Resour Health. 2019 Jan 15;17(1):6.

        BACKGROUND: Shortage of health workforce in most African countries is a major impediment to achieving health and development goals. Countries are encouraged to develop evidence-based strategies to scale up their health workforce in order to bridge the gap. South-South collaborations have gained popularity due to similarities in the challenges faced in the region. This strategy has been used in trade, education, and health sector among others. This paper is a road map of using a South-South collaboration to develop a Human Resources Information System (HRIS) to inform scale-up of the health workforce. CASE PRESENTATION: In the last decade, Kenya implemented one of the most comprehensive HRIS in Africa. The HRIS was funded by the US President’s Emergency Plan for AIDS Relief (PEPFAR) through the Centers for Disease Control and Prevention (CDC) and implemented by Emory University. The Kenyan team collaborated with the Zambian team to establish a similar HRIS in Zambia. This case study describes the collaboration activities between Zambia and Kenya which included needs assessment, establishment of project office, stakeholders’ sensitization, technical assistance and knowledge transfer, software reuse, documents and guidelines reuse, project structure and management, and project formative evaluation. Furthermore, it highlights the need for adopting effective communication strategies, collaborative planning, teamwork, willingness to learn, and having minimum technical skills from the recipient country as lessons learned from the collaboration. As a result of the collaboration, while Kenya took 5 years, Zambia was able to implement the project within 2 years which is less than half the time it took Kenya. CONCLUSIONS: This case presents a unique experience in the use of South-South collaboration in establishing a HRIS. It illustrates the steps and resources needed while identifying the successes and challenges in undertaking such collaboration.

    • Substance Use and Abuse
      1. Opioid prescribing rates in nonmetropolitan and metropolitan counties among primary care providers using an electronic health record system – United States, 2014-2017External
        Garcia MC, Heilig CM, Lee SH, Faul M, Guy G, Iademarco MF, Hempstead K, Raymond D, Gray J.
        MMWR Morb Mortal Wkly Rep. 2019 Jan 18;68(2):25-30.

        Drug overdose is the leading cause of unintentional injury-associated death in the United States. Among 70,237 fatal drug overdoses in 2017, prescription opioids were involved in 17,029 (24.2%) (1). Higher rates of opioid-related deaths have been recorded in nonmetropolitan (rural) areas (2). In 2017, 14 rural counties were among the 15 counties with the highest opioid prescribing rates.* Higher opioid prescribing rates put patients at risk for addiction and overdose (3). Using deidentified data from the Athenahealth electronic health record (EHR) system, opioid prescribing rates among 31,422 primary care providers(dagger) in the United States were analyzed to evaluate trends from January 2014 to March 2017. This analysis assessed how prescribing practices varied among six urban-rural classification categories of counties, before and after the March 2016 release of CDC’s Guideline for Prescribing Opioids for Chronic Pain (Guideline) (4). Patients in noncore (the most rural) counties had an 87% higher chance of receiving an opioid prescription compared with persons in large central metropolitan counties during the study period. Across all six county groups, the odds of receiving an opioid prescription decreased significantly after March 2016. This decrease followed a flat trend during the preceding period in micropolitan and large central metropolitan county groups; in contrast, the decrease continued previous downward trends in the other four county groups. Data from EHRs can effectively supplement traditional surveillance methods for monitoring trends in opioid prescribing and other areas of public health importance, with minimal lag time under ideal conditions. As less densely populated areas appear to indicate both substantial progress in decreasing opioid prescribing and ongoing need for reduction, community health care practices and intervention programs must continue to be tailored to community characteristics.

      2. Coverage of nonpharmacologic treatments for low back pain among US public and private insurersExternal
        Heyward J, Jones CM, Compton WM, Lin DH, Losby JL, Murimi IB, Baldwin GT, Ballreich JM, Thomas DA, Bicket MC, Porter L, Tierce JC, Alexander GC.
        JAMA Netw Open. 2018 Oct 5;1(6):e183044.

        Importance: Despite epidemic rates of addiction and death from prescription opioids in the United States, suggesting the importance of providing alternatives to opioids in the treatment of pain, little is known regarding how payers’ coverage policies may facilitate or impede access to such treatments. Objective: To examine coverage policies for 5 nonpharmacologic approaches commonly used to treat acute or chronic low back pain among commercial and Medicare Advantage insurance plans, plus an additional 6 treatments among Medicaid plans. Design, Setting, and Participants: Cross-sectional study of 15 commercial, 15 Medicaid, and 15 Medicare Advantage health plans for the 2017 calendar year in 16 states representing more than half of the US population. Interviews were conducted with 43 senior medical and pharmacy health plan executives from representative plans. Main Outcomes and Measures: Medical necessity and coverage status for the treatments examined, as well as the use of utilization management tools and cost-sharing magnitude and structure. Results: Commercial and Medicare insurers consistently regarded physical and occupational therapy as medically necessary, but policies varied for other therapies examined. Payers most commonly covered physical therapy (98% [44 of 45 plans]), occupational therapy (96% [43 of 45 plans]), and chiropractic care (89% [40 of 45 plans]), while transcutaneous electrical nerve stimulation (67% [10 of 15 plans]) and steroid injections (60% [9 of 15 plans]) were the most commonly covered among the therapies examined for Medicaid plans only. Despite evidence in the literature to support use of acupuncture and psychological interventions, these therapies were either not covered by plans examined (67% of all plans [30 of 45] did not cover acupuncture) or lacked information about coverage (80% of Medicaid plans [12 of 15] lacked information about coverage of psychological interventions). Utilization management tools, such as prior authorization, were common, but criteria varied greatly with respect to which conditions and what quantity and duration of services were covered. Interviewees represented 6 Medicaid managed care organizations, 2 Medicare Advantage or Part D plans, 9 commercial plans, and 3 trade organizations (eg, Blue Cross Blue Shield Association). Interviews with plan executives indicated a low level of integration between the coverage decision-making processes for pharmacologic and nonpharmacologic therapies for chronic pain. Conclusions and Relevance: Wide variation in coverage of nonpharmacologic treatments for low back pain may be driven by the absence of best practices, the administrative complexities of developing and revising coverage policies, and payers’ economic incentives. Such variation suggests an important opportunity to improve the accessibility of services, reduce opioid use, and ultimately improve the quality of care for individuals with chronic, noncancer pain while alleviating the burden of opioid addiction and overdose.

      3. Prescription drug coverage for treatment of low back pain among US Medicaid, Medicare Advantage, and commercial insurersExternal
        Lin DH, Jones CM, Compton WM, Heyward J, Losby JL, Murimi IB, Baldwin GT, Ballreich JM, Thomas DA, Bicket M, Porter L, Tierce JC, Alexander GC.
        JAMA Netw Open. 2018 Jun 1;1(2):e180235.

        Importance: Despite unprecedented injuries and deaths from prescription opioids, little is known regarding medication coverage policies for the treatment of chronic noncancer pain among US insurers. Objective: To assess medication coverage policies for 62 products used to treat low back pain. Design, Setting, and Participants: A cross-sectional study of health plan documents from 15 Medicaid, 15 Medicare Advantage, and 20 commercial health plans in 2017 from 16 US states representing more than half the US population and 20 interviews with more than 43 senior medical and pharmacy health plan executives from representative plans. Data analysis was conducted from April 2017 to January 2018. Main Outcomes and Measures: Formulary coverage, utilization management, and patient out-of-pocket costs. Results: Of the 62 products examined, 30 were prescription opioids and 32 were nonopioid analgesics, including 10 nonsteroidal anti-inflammatory drugs, 10 antidepressants, 6 muscle relaxants, 4 anticonvulsants, and 2 topical analgesics. Medicaid plans covered a median of 19 opioids examined (interquartile range [IQR], 12-27; median, 63%; IQR, 40%-90%) and a median of 22 nonopioids examined (IQR, 21-27; median, 69%; IQR, 66%-83%). Medicare Advantage plans covered similar proportions (median [IQR], opioids: 17 [15-22]; 57% [50%-73%]; nonopioids: 22 [22-26]; 69% [69%-81%]), while commercial plans covered more opioids (median [IQR], 23 [21-25]; 77% [70%-84%]) and nonopioids (median [IQR], 26 [24-27]; 81% [74%-85%]). Utilization management strategies were common for opioids in Medicaid plans (median [IQR], 15 [11-20] opioids; 91% [74%-97%]), Medicare Advantage plans (median [IQR], 15 [9-18] opioids; 100% [100%-100%]), and commercial plans (median [IQR], 16 [11-20] opioids; 74% [53%-94%]), generally relying on 30-day quantity limits rather than prior authorization. Step therapy was especially uncommon. Many of the nonopioids examined also were subject to utilization management, especially quantity limits (24%-32% of products across payers) and prior authorization (median [IQR], commercial plans: 2 [0-3] nonopioids; 9% [0%-11%]; Medicare Advantage plans: 4 [3-5] nonopioids; 19% [10%-23%]; Medicaid plans: 6 [1-13] nonopioids; 38% [2%-52%]). Among commercial plans, the median plan placed 18 opioids (74%) and 20 nonopioids (81%) in tier 1, which was associated with a median out-of-pocket cost of $10 (IQR, $9-$10) per 30-day supply. Key informant interviews revealed an emphasis on increasing opioid utilization management and identifying high-risk prescribers and patients, rather than promoting comprehensive strategies to improve treatment of chronic pain or better integrating pharmacologic and nonpharmacologic alternatives to opioids. Conclusions and Relevance: Given the effect of coverage policies on drug utilization and health outcomes, these findings provide an important opportunity to evaluate how formulary placement, utilization management, copayments, and integration of nonpharmacologic treatments can be optimized to improve pain care while reducing opioid-related injuries and deaths.

      4. Biochemically confirmed smoking cessation and gestational weight gainExternal
        Rockhill KM, England LJ, Tong VT, Sharma AJ.
        Birth. 2019 Jan 11.

        BACKGROUND: Prenatal smoking cessation has substantial health benefits for mothers and offspring, but concerns about weight gain may be a barrier to quitting. We quantified gestational weight gain associated with biochemically confirmed smoking cessation. METHODS: Data originated from a randomized controlled cessation trial: Smoking Cessation in Pregnancy project (1987-1991). We calculated gestational weight gain using self-reported prepregnancy weight and measured weight at 30-34 weeks of gestation. We used linear regression to estimate adjusted mean differences in gain for quitters versus continuing smokers by the last trimester. The effects of quitting earlier (by 2nd trimester) versus later (by 3rd trimester) were calculated. We assessed the percentages who gained weight according to Institute of Medicine (IOM) recommendations within 2 weeks of a full-term delivery. RESULTS: At 30-34 weeks, nulliparous and multiparous quitters gained an average of 3.0 pounds (95% CI 0.9-5.1 pounds) (1.4 kg [0.4-2.3 kg]) and 6.6 pounds (95% CI 4.3-8.9 pounds) (3.0 kg [1.9-4.0 kg]) more, respectively, than continuing smokers. Weight gain in early quitters did not differ significantly from that in late quitters. Quitters were more likely than continuing smokers to gain above current guidelines (60.3% vs 46.3%) and were less likely to gain below guidelines (11.5% vs 21.6%) (P = 0.002). CONCLUSIONS: Although quitters had modest additional weight gain by 30-34 weeks compared to continuing smokers, a high proportion in both groups gained in excess of IOM recommendations. Both quitters and continuing smokers may need support to achieve optimal gestational weight gain.

      5. Notes from the Field: Fentanyl drug submissions – United States, 2010-2017External
        Springer YP, Gladden RM, O’Donnell J, Seth P.
        MMWR Morb Mortal Wkly Rep. 2019 Jan 18;68(2):41-43.

        [No abstract]

    • Zoonotic and Vectorborne Diseases
      1. Risk factors for hospitalization of patients with chikungunya virus infection at sentinel hospitals in Puerto RicoExternal
        Hsu CH, Cruz-Lopez F, Vargas Torres D, Perez-Padilla J, Lorenzi OD, Rivera A, Staples JE, Lugo E, Munoz-Jordan J, Fischer M, Garcia Gubern C, Rivera Garcia B, Alvarado L, Sharp TM.
        PLoS Negl Trop Dis. 2019 Jan 14;13(1):e0007084.

        BACKGROUND: Hospitalization of patients during outbreaks of chikungunya virus has been reported to be uncommon (0.5-8.7%), but more frequent among infants and the elderly. CHIKV was first detected in Puerto Rico in May 2014. We enrolled patients with acute febrile illness (AFI) presenting to two hospital emergency departments in Puerto Rico and tested them for CHIKV infection to describe the frequency of detection of CHIKV-infected patients, identify risk factors for hospitalization, and describe patients with severe manifestations. METHODOLOGY/PRINCIPAL FINDINGS: Serum specimens were collected from patients with AFI and tested by rRT-PCR. During May-December 2014, a total of 3,035 patients were enrolled, and 1,469 (48.4%) had CHIKV infection. A total of 157 (10.7%) CHIKV-infected patients were hospitalized, six (0.4%) were admitted to the intensive care unit, and two died (0.1%). Common symptoms among all CHIKV-infected patients were arthralgia (82.6%), lethargy (80.6%), and myalgia (80.5%). Compared to patients aged 1-69 years (7.3%), infant (67.2%) and elderly (17.3%) patients were nine and two times more likely to be hospitalized, respectively (relative risk [RR] and 95% confidence interval [CI] = 9.16 [7.05-11.90] and 2.36 [1.54-3.62]). Multiple symptoms of AFI were associated with decreased risk of hospitalization, including arthralgia (RR = 0.31 [0.23-0.41]) and myalgia (RR = 0.29 [0.22-0.39]). Respiratory symptoms were associated with increased risk of hospitalization, including rhinorrhea (RR = 1.68 [1.24-2.27) and cough (RR = 1.77 [1.31-2.39]). Manifestations present among <5% of patients but associated with patient hospitalization included cyanosis (RR = 2.20 [1.17-4.12) and seizures (RR = 3.23 [1.80-5.81). DISCUSSION: Among this cohort of CHIKV-infected patients, hospitalization was uncommon, admission to the ICU was infrequent, and death was rare. Risk of hospitalization was higher in patients with symptoms of respiratory illness and other manifestations that may not have been the result of CHIKV infection.

      2. Reassessing serosurvey-based estimates of the symptomatic proportion of Zika virus infectionsExternal
        Mitchell PK, Mier-y-Teran-Romero L, Biggerstaff BJ, Delorey MJ, Aubry M, Cao-Lormeau VM, Lozier MJ, Cauchemez S, Johansson MA.
        Am J Epidemiol. 2019 Jan 1;188(1):206-213.

        Since the 2007 Zika epidemic in the Micronesian state of Yap, it has been apparent that not all people infected with Zika virus (ZIKV) experience symptoms. However, the proportion of infections that result in symptoms remains unclear. Existing estimates have varied in their interpretation of symptoms due to other causes and the case definition used, and they have assumed perfect test sensitivity and specificity. Using a Bayesian model and data from ZIKV serosurveys in Yap (2007), French Polynesia (2013-2014), and Puerto Rico (2016), we found that assuming perfect sensitivity and specificity generally led to lower estimates of the symptomatic proportion. Incorporating reasonable assumptions for assay sensitivity and specificity, we estimated that 27% (95% credible interval (CrI): 15, 37) (Yap), 44% (95% CrI: 26, 66) (French Polynesia), and 50% (95% CrI: 34, 92) (Puerto Rico) of infections were symptomatic, with variation due to differences in study populations, study designs, and case definitions. The proportion of ZIKV infections causing symptoms is critical for surveillance system design and impact assessment. Here, we accounted for key uncertainties in existing seroprevalence data and found that estimates for the symptomatic proportion ranged from 27% to 50%, suggesting that while the majority of infections are asymptomatic or mildly symptomatic, symptomatic infections might be more common than previously estimated.

      3. Dengue virus is an under-recognised causative agent of acute encephalitis syndrome (AES): Results from a four year AES surveillance study of Japanese encephalitis in selected states of IndiaDengue virus is an under-recognised causativeExternal
        Ravi V, Hameed SK, Desai A, Mani RS, Reddy V, Velayudhan A, Yadav R, Jain A, Saikia L, Borthakur AK, Mohan DG, Bhandopadhyay B, Bhattacharya N, Dhariwal AC, Sen PK, Venkatesh S, Prasad J, Laserson K, Srikantiah P.
        Int J Infect Dis. 2019 Jan 11.

        BACKGROUND: Acute encephalitis syndrome (AES) surveillance in India has indicated that Japanese encephalitis virus (JEV) accounts for 5-35% of AES cases annually; the etiology remains unknown in the remaining cases. We implemented comprehensive AES surveillance to identify other etiological agents of AES, with emphasis on dengue virus. METHODS: Serum and cerebrospinal fluid (CSF) specimens were collected from patients enrolled prospectively in AES surveillance from 2014-2017 at selected sites of three high burden states of India. All samples were initially tested for JEV IgM. Specimens negative for JEV by serology were tested for IgM to scrub typhus, dengue virus (DEN), and West Nile virus; all JEV IgM-negative CSF samples were tested by PCR for S.pneumoniae, N.meningitidis, H.influenzae, herpes simplex virus type 1, enteroviruses and DEN. RESULTS: Of 10,107 AES patients, an etiology could be established in 49.2% of patients including JEV (16%), scrub typus (16%) and DEN (5.2%) as the top three agents. Amongst the DEN positive cases (359/6892), seven (2%) were positive only for dengue virus RNA: one in serum and six in CSF. CONCLUSION: Amongst the pathogens identified, dengue accounted for 5% of all AES cases and was one of the three common etiological agents. These results underscore the importance of including dengue virus in routine testing of AES cases.

      4. Incidence and outcome of severe and nonsevere thrombocytopenia associated with Zika virus infection – Puerto Rico, 2016External
        Van Dyne EA, Neaterour P, Rivera A, Bello-Pagan M, Adams L, Munoz-Jordan J, Baez P, Garcia M, Waterman SH, Reyes N, Richardson LC, Rivera-Garcia B, Sharp TM.
        Open Forum Infect Dis. 2019 Jan;6(1):ofy325.

        Background: Zika virus (ZIKV) infection has been associated with severe thrombocytopenia. We describe the incidence, clinical manifestations, and outcomes of patients with ZIKV infection and thrombocytopenia. Methods: We reviewed medical records of patients with ZIKV infection and thrombocytopenia (platelet count <100 x10(9) cells/L) in Puerto Rico during 2016. Severe thrombocytopenia was defined by platelet count <20 x10(9)/L or a platelet count <50 x10(9)/L and treatment for immune thrombocytopenia (ITP). Results: Of 37 878 patients with ZIKV infection, 47 (0.1%) had thrombocytopenia in the absence of an alternative etiology (1.4 cases/100 000 population), including 12 with severe thrombocytopenia. Most patients with thrombocytopenia were adult (77%) and male (53%). Platelet nadir occurred a median (range) of 6 (1-16) and 5 (0-34) days after symptom onset for patients with severe and nonsevere thrombocytopenia, respectively. Among patients with severe thrombocytopenia, all had bleeding, 33% were admitted to the intensive care unit, and 8% died; 50% were treated for ITP. Among 5 patients with severe thrombocytopenia who received intravenous immunoglobulin, the median platelet count increase (range) was 112 (65-202) x10(9)/L. In contrast, among 4 patients who received platelet transfusion, the median increase in platelet count (range) was 8.5 (-6 to 52) x10(9)/L. Conclusions: Patients with severe thrombocytopenia and ZIKV infection experienced prominent acute morbidity. Consistent with recommended management, administration of ITP treatments to such patients may be more efficacious than platelet transfusion in resolving thrombocytopenia. Severe thrombocytopenia should be considered a rare outcome of ZIKV infection.

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